This  Copy  is  No 


^-ro 


PAPERS  AND  ADDRESSES 

BY 
WILLIAM  HENRY  WELCH 


PAPERS  AND  ADDRESSES 

BY 

WILLIAM  HENRY  WELCH 


IN  THREE  VOLUMES 


Vol.  I 
PATHOLOGY 


PREVENTIVE  MEDICINE 


BALTIMORE 

THE  JOHNS  HOPKINS  PRESS 

MDCCCCXX 


ZU  Bovi  <§a(timovi  (prece 

BALTIMORE,  UD.,   U.  8.   A. 


iiiemedica] 
Library 

w 

7 


IN  HONOR  OF 

WILLIAM  HENRY  WELCH 

UPON 

THE  SEVENTIETH  ANNIVERSARY  OF  HIS  BIRTH 

THIS  COLLECTED  EDITION 

OF  HIS  PAPERS  AND  ADDRESSES  IS  PUBLISHED 

AS  A  TOKEN  OF  AFFECTION,   GRATITUDE  AND  ESTEEM 

BY  HIS  ASSOCIATES  AND  PUPILS 


^'06763 


EDITORIAL  NOTE 

On  the  eighth  of  last  April  Dr.  Welch  attained  his  seventieth 
birthday.  To  many  of  his  friends  it  seemed  that  such  an 
occasion  ought  not  to  pass  without  some  manifestation  of 
affection  and  admiration  on  the  part  of  the  medical  profession 
of  America  to  one  who  has  long  stood  as  its  leader,  and  that 
a  worthy  expression  would  bfe  the  preservation  in  suitable  form 
of  the  chief  contributions  from  his  pen. 

Dr.  Welch's  writings  are  scattered  through  a  great  variety 
of  publications,  many  of  which  are  more  or  less  inaccessible. 
It  was  accordingly  decided  to  bring  together  and  to  publish 
the  more  important  of  his  numerous  papers  and  addresses  of 
the  past  forty-two  years,  publications  which  reveal  the  great 
part  he  has  played  in  the  development  of  medical  science  and 
medical  education. 

With  the  permission  of  Dr.  Welch,  the  editor,  in  his  student 
days,  had  collected  these  papers  and  addresses  with  a  view  to 
republication.  When  it  became  evident  that  the  work  would 
be  interrupted  by  the  war  the  appended  Bibliography  was 
published.  On  his  return  from  France  after  the  Armistice  the 
editor  was  invited  by  the  Publication  Committee  to  undertake, 
under  its  supervision,  the  editing  of  these  volumes. 

The  collected  material  covers  a  period  during  which  there 
have  been  great  advances  in  medicine,  especially  through  the 
impetus  following  the  development  of  cellular  pathology,  the 
discovery  and  study  of  pathogenic  microorganisms,  and  the 
more  widespread  adoption  of  experimental  methods.  It  will 
be  noted  that  a  number  of  the  papers,  and  especially  addresses 
and  discussions,  are  from  stenographic  reports.  Some  of 
these  have  been  revised  and  given  appropriate  titles,  but  no 
attempt  has  been  made  in  these  or  other  articles  to  alter  the 
subject  matter  so  as  to  bring  it  up  to  the  later  state  of  knowl- 
edge.   In  view  of  the  fact  that  these  publications  have  appeared 


in  England,  Germany,  and  America  during  a  period  covering 
nearly  a  half  century,  the  orthography  is  not  consistent  through- 
out the  volumes. 

The  volumes  include  studies  in  pathology,  preventive  medi- 
cine, bacteriology,  medical  education,  the  relation  of  medicine 
to  other  sciences,  and  the  history  of  medicine  in  the  United 
States  and  elsewhere.  Papers  on  similar  subjects,  although 
scattered  over  a  number  of  years,  have  been  placed  together 
chronologically  in  groups. 

In  behalf  of  the  Publication  Committee  the  editor  desires  to 
thank  the  editors  and  publishers  of  books  and  periodicals  for 
their  hearty  cooperation  in  consenting  to  the  use  of  articles 
appearing  in  these  volumes.  Especial  thanks  are  due  to 
Sir  Clifford  Allbutt  of  Cambridge,  England;  Dr.  Frederic  S. 
Dennis,  New  York ;  the  Macmillan  Company,  London ;  Lea  and 
Febiger,  Philadelphia;  to  the  editors  of  the  Bulletin  of  The 
Johns  Hopkins  Hospital,  the  Transactions  of  the  Association 
of  American  Physicians,  the  Journal  of  the  American  Medical 
Association,  the  Bulletin  of  the  Medical  and  Chirurgical 
Faculty  of  Maryland,  the  Maryland  Medical  Journal,  the  Jour- 
nal of  Experimental  Medicine,  Science,  and  numerous  other 
publications;  and  to  Mr.  Max  Broedel,  who  has  redrawn  some  of 
tlie  illustrations. 

It  is  largely  through  the  active  interest  and  advice  of 
Dr.  William  Stewart  Halsted  and  Dr.  Henrj'  M.  Kurd  in  every 
phase  of  the  publication  that  this  tribute  to  Dr.  Welch  has  come 
to  pass.  A  great  debt  of  appreciation  is  due  to  Dr.  Simon 
Flexner  for  his  preparation  of  the  Introduction.  To  Lieut.  Col. 
Fielding  H.  Garrison,  M.  C,  U.  S.  Army,  Dr.  William  Sydney 
Thayer,  Dr.  William  G.  MacCallum,  Dr.  John  Howland,  Dr.  Lew- 
ellys  F.  Barker,  Dr.  J.  Whitridge  Williams,  Dr.  Ralph  B.  Seem, 
Miss  Minnie  Blogg,  The  Johns  Hopkins  Press,  Mr.  Nathan 
Billstein  of  the  Lord  Baltimore  Press,  and  many  other  friends 
of  the  author  who  have  given  valuable  assistance  the  editor 
expresses  his  indebtedness. 

Walter  C.  Burket. 

PKrEMBER    1920. 


TABLE  OF  CONTENTS 

PAGE 

Introduction    xi 

PATHOLOGY 

Zur  Pathologie  des  Lungenodems 3 

Theor}'  of  Pulmonary  Oedema 36 

The  Behaviour  of  the  Red  Blood-Corpuscles  when  Shaken  with  Indiffer- 
ent  Substances 42 

The  Structure  of  White  Thrombi 47 

Hemorrhagic  Infarction 6Q 

Experimental  Study  of  Haemorrhagic  Infarction  of  the  Small  Intestine 

in  the  Dog 77 

Thrombosis 110 

Embolism    193 

Venous  Thrombosis  in  Cardiac  Disease 259 

Miliary  Aneurism  of  a  Branch  of  the  Gastric  Artery 285 

Duplicature  of  Arch  of  Aorta  with  Aneurism 286 

Sudden  Deaths  from  Cardiac  Disease 288 

An  Experimental  Study  of  Glomerulo-Nephritis 293 

The  Cartwright  Lectures.    On  the  General  Pathology  of  Fever 302 

Hyperthermy  in  Man 367 

Adaptation  in  Pathological  Processes 370 

Hydrophobia   395 

Cirrhosis  Hepatis  Anthracotica 408 

The  Pathological  Effects  of  Alcohol 413 

Osteo-Fibromyoma  of  the  Uterus 432 

Medullary  Form  of  Sarcoma  of  the  Sternum,  with  Metastases  in  the 

Lymphatic  Glands 434 

Diffuse  Infiltrating  Carcinoma  of  the  Stomach 440 

Syringo-Cystoma   444 

Chronic  Jaundice  with  Xanthoma  Multiplex 447 

Chronic  Peritonitis  with  Complete  Obstruction,  Caused  by  Numerous 
Constrictions  of  a  Previously  Undescribed  Character,  Throughout 

the  Intestine 449 

Idiopathic  Phlegmonous  Gastritis 457 

ix 


X  TABLE  OF  CONTENTS 

PAGK 

The  Effusion  of  Chyle  and  of  Chyle-Like  Milky,  Fatty,  and  Oily  Fluids 

into  the  Serous  Cavities 458 

Catheterization  of  the  Ureters  in  the  Male 460 

Primary  Echinococcus  Cysts  of  the  Pleura 461 

Malaria  • 463 

So-Callod  Parasitic  Bodies  in  Epithelioma 532 

The  Parasite  of  Cancer 534 

Exhibition  of  Animal  Parasites 536 

Intestinal  and  Hepatic  Actinomycosis,  Associated  with  Leukaemia.  . .  .  541 

PREVENTIVE  MEDICINE 

Modes  of  Infection  549 

Considerations   Concerning  Some   External   Sources   of  Infection   in 

Their  Bearing  on  Preventive  Medicine 567 

Sanitation  in  Eelation  to  the  Poor 588 

Asiatic  Cholera  in  its  Relations  to  Sanitary  Reforms 599 

The  Relation  of  Sewage  Disposal  to  Public  Health 60T 

Relations  of  Laboratories  to  Public  Health 615 

Duties  of  a  Hospital  to  the  Public  Health 621 

Opening  Remarks  by  the  President  of  the  Section  on  Pathology  and 

Bacteriology   of   Tul)erculosis 629 

What  May  be  Expected  from  More  Effective  Application  of  Preventive 

Measures  Against  Tuberculosis 632 

Considerations  Relating  to  the  Control  of  Tuberculosis 637 

The  Significance  of  the  Great  Frequency  of  Tuberculous  Infection  in 

Early  Life  for  Prevention  of  the  Disease 640 

Control  of  Bovine  Tuberculosis 651 

Cliild  Welfare 655 

Institute  of  Hygiene 660 

The   School   of   Hygiene   and    Pul)lic    Health   at  the  Johns   Hopkins 

University   669 

Remarks  at  Opening  of  Medical  Conference  of  Red  Ctoss  Societies.  . . .  672 
Scope  of  the  Proposed  Health  Activities  of  the  League  of  Red  Cross 

Societies    674 


WILLIAM  HENRY  WELCH 

A  BIOGRAPHICAL  SKETCH 

My  Deae  Associates  : 

On  this  memorable  and  beautiful  occasion  I  have  the  cherished  honor  of 
having  been  chosen  to  perform,  as  it  were,  the  duties  of  chronicler,  in  order 
that  we  may  all  be  led  to  review  in  our  minds  the  successive  steps  by  which 
our  great  leader  and  master  rose  to  such  high  distinction  and  ^vrought  the 
miracle  of  giving  to  medicine  a  new  birth  in  this  country;  and  in  order, 
also,  that  our  successors,  lighting  their  lamps  at  the  shrine  of  Pathology 
and  studying  the  treasures  which  these  precious  volumes  enclose,  may  catch 
a  gleam  of  what  manner  of  man  he  was  who  produced  them,  and  who  by  the 
vigor  of  his  living  example  and  the  charm  of  a  rare  personality,  as  well  as 
by  the  power  of  his  spoken  and  written  word,  in  the  short  span  of  a  lifetime 
raised  medicine  in  the  United  States  from  a  beneficent  art  to  an  expanding 
science. 

William  Henry  Welch  was  born  in  Norfolk,  Connecticut,  April  8,  1850. 
He  was  the  son  of  William  and  Emeline  (Collin)  Welch.  His  father  was 
a  practising  physician,  as  were  four  of  his  father's  brothers.  Moreover,  a 
great  grandfather  and  grandfather  were  also  physicians.  When  about  one 
year  of  age,  William  Henry's  mother  died ;  thereafter  he  was  taken  care  of 
and  brought  up  by  his  paternal  grandmother,  who  resided  with  the  father. 
A  contemporary  describes  the  youth  as  a  great  favorite  in  the  village,  inter- 
ested in  all  kinds  of  sports  and  athletic  exercises.  During  the  Civil  War,  the 
youthful  William  became  captain  of  a  company  of  zouaves,  who,  dressed 
in  regulation  costume  and  provided  with  guns,  drilled  regularly  on  the 
village  green.  When  about  twelve  years  old,  William  was  sent  to  a  nearby 
boarding  school  at  Winchester  Centre,  conducted  by  the  Eeverend  Ira  W. 
Pettibone,  an  uncle  by  marriage.  Here  he  prepared  for  Yale  College  which 
he  entered  in  1866,  in  his  sixteenth  year,  and  from  which  he  was  graduated 
in  1870,  with  the  A.  B,  degree,  standing  third  in  his  class.  During  his 
college  period  he  impressed  his  teachers  and  classmates  with  the  possession 
of  the  gifts  which  afterwards  distinguished  him  in  so  large  a  measure.  After 
graduation  and  before  entering  upon  his  medical  studies,  Welch  taught 
school  for  one  year  at  Norwich,  New  York. 

Thus  it  was  in  his  twenty-first  year  that  Welch  matriculated  at  the  College 
of  Physicians  and  Surgeons,  in  New  York  City.  But  this  first  venture  into 
2  xi 


zu 


INTRODUCTION 


medicine  was  very  brief.  An  almost  prophetic  vision  into  the  future  gave 
him  pause  and  led  to  his  return  to  New  Haven  for  a  year  of  study  in  chem- 
istry, which  field  even  at  that  early  date  he  perceived  to  hold  great  future 
possibilities  for  the  study  of  medicine.  This  intermediate  year  was  spent 
jointly  at  the  Sheffield  Scientific  School  and  at  the  Yale  Medical  School. 
In  the  former,  Welch  came  under  the  influence  of  Professor  Oscar  H.  Allen 
who  strongly  stimulated  his  interest  in  science  in  general  and  in  chemistry 
in  particular.  This  rather  unconventional  and  solitary  personality,  who  was 
not  only  chemist,  but  geologist,  mineralogist  and  botanist  as  weU,  proved 
to  be  an  inspiring  teacher.  At  the  Yale  Medical  School  the  professor  of  chem- 
istry was  George  Frederic  Barker,  afterwards  professor  of  physics  at  the  Uni- 
versity of  Pennsylvania  and  a  member  of  the  National  Academy  of  Sciences, 
who  was  deeply  interested  at  the  time  in  organic  chemistry  and  thus  turned 
his  pupil's  attention  to  the  writings  of  Kekule  which  were  Just  then  exerting 
a  dominant  influence  on  chemical  thought.  Within  the  year  the  student  was 
mastering  the  concepts  of  Kekule  in  the  original  German.  The  breadth  of 
interest  of  the  two  able  teachers  under  whom  Welch  had  the  good  fortune 
to  come  during  this  preparatorj'  year,  may  well  have  exercised  a  directive  if 
latent  influence  on  the  gifted  and  impressionable  pupil  which  at  a  somewhat 
distant  day  was  to  assert  itself  in  the  determination  to  break  with  the  tra- 
ditional and  alluring  career  of  private  and  consultative  practice,  and  to 
embark  upon  the  hazardous  one  of  pathology.  This  decision  was  not,  however, 
arrived  at  immediately  or  even  at  the  outset  of  his  medical  work,  but  came 
later  as  part  of  a  widening  knowledge  and  an  enlarging  experience. 

It  was  fated  also  that  the  two  men  who,  each  in  his  own  although  different 
way,  were  to  influence  the  rise  of  pathology  in  the  United  States,  should 
first  come  together  in  the  chemical  laboratory  of  the  Sheffield  Scientific 
School.  T.  Mitchell  Prudden  had  gone  through  the  School  at  about  the  time 
wlien  William  II.  Welch  passed  through  the  College ;  but  as  in  that  day  the 
two  sets  of  students — academic  and  scientific — rarely  met  and  never  mingled, 
the  two  men  were  not  brought  into  contact.  W^hen  Welch  entered  the  labora- 
tory, Prudden  was  already  there,  filling  a  kind  of  voluntary  instructorship ; 
and  thus  the  two  men  whose  paths  were  to  cross  and  recross  in  the  many 
subsequent  years  of  sympathy,  perfect  understanding  and  common  endeavor, 
first  discovered  in  each  other,  albeit  still  in  embryo  as  it  were,  that  devotion 
to  science  and  its  ideals  which  as  the  years  lengthened  was  to  prove  secure 
against  the  many  and  insistent  allurements  and  pecuniary  rewards  of  medical 
practice. 

The  year  of  chemical  study  over,  Welch  returned  definitely  to  his  medical 
studies.  It  will  aid  us  a  little  later  in  the  understanding  of  the  change  about 
to  be  wrought  in  the  pursuit  of  pathology — in  the  making  of  advances  in 


INTEODUCTION  xiii 

which  the  then  unsuspecting  medical  student  was  to  play  so  large  a  part — if 
we  pause  to  sketch  in  broad  outline  the  kind  of  educational  discipline  offered 
the  medical  student  at  the  College  of  Physicians  and  Surgeons,  a  leading 
institution,  in  the  period  embraced  by  the  years  1872  to  1875. 

In  1872,  when  Welch  entered,  the  College  of  Physicians  and  Surgeons 
had  been  in  operation  for  sixty-five  years  and  led  all  its  competitors  in  the 
number  of  its  students  and  in  teaching  facilities.  The  College  occupied  a 
building  of  its  own  on  Twenty-third  Street,  regarded  as  commodious,  and 
was  a  part  of  Columbia  University.  The  term  of  instruction  had  been 
extended  from  four  to  five  months,  and  three  instead  of  two  sessions  of 
attendance  upon  lectures  were  required  for  graduation.  The  precarious 
supply  of  material  for  dissection  and  for  instruction  in  operative  surgery 
and  the  method  of  obtaining  it  had  been  superseded  and  made  fairly  adequate 
by  legal  enactment.  The  courses  in  anatomy  and  to  a  less  degree  those  in 
medical  chemistry  comprised  the  entire  provision  for  objective  or  practical 
teaching,  aside  from  the  out-patient  clinic  at  the  College  and  the  clinical 
lectures  given  at  the  New  York  and  Bellevue  Hospitals  and  the  Almshouse. 
A  voluntary  course  of  lectures  on  pathological  anatomy  with  demonstration 
of  organs  removed  at  autopsy  was  offered  during  the  summer  session  by 
Francis  Delafield. 

While  the  preceptorial  system  was  still  in  vogue  and  the  medical  student 
was  still  expected  to  obtain  the  main  part  of  his  clinical  training  during  the 
long  interval  between  sessions,  in  the  office  and  on  the  rounds  of  his  preceptor, 
the  few  outstanding  students  could  hope  to  enter  Bellevue  Hospital  for  an 
interneship,  which  might  begin  even  six  months  before  graduation.  But 
the  didactic  lectui^e,  of  which  the  instruction  still  chiefly  consisted,  was 
expected  to  fill  the  mind  of  the  student  with  the  medical  lore  of  the  day, 
while  it  served  also  to  impress  his  imagination  with  the  vigorous  personality 
and  high  authority  of  the  eminent  teachers  under  whom  he  sat,  in  a  manner 
now  wholly  foreign  to  the  spirit  of  medical  teaching. 

But  to  the  able,  energetic  and  ambitious  student  the  plan,  imperfect  as 
it  was  as  an  educational  discipline,  admitted  of  a  choice  of  subject  and 
disposition  of  effort  not  contemplated  in  the  system.  And  thus  we  find  Welch 
in  the  early  period  of  his  medical  studies  enticed  away  from  the  lecture  halls 
into  the  more  alluring  atmosphere  of  the  dissecting  room  and  very  soon 
serving  as  prosector  to  the  professors  of  anatomy. 

With  the  curriculum  as  indicated,  it  is  obvious  that  no  opportunity  existed 
to  acquire  thorough  training  in  any  subject,  aside  possibly  from  the  grosser 
aspects  of  human  anatomy.  The  provision  for  pathology  was  extremely 
meagre.  Although  a  chair  of  physiology  and  pathology,  filled  by  Alonzo 
Clark,  had  been  created  in  1847,  in  the  early  seventies  of  the  last  century. 


liv  INTEODUCTION 

pathology  had  not  become  an  independent  subject  of  teaching,  but  was 
attached  to  the  chair  of  medicine,  still,  as  it  happened,  under  Doctor 
Clark,  who  had  been  transferred  to  the  professorship  of  pathology  and 
clinical  medicine. 

There  is  no  reason  to  suppose  that  Clark  treated  pathologj"^  otherwise 
than  by  lectures,  with  perhaps  at  most  the  occasional  use  of  specimens  from 
the  deadhouse.  On  the  other  hand,  Francis  Delafield,  who  had  become 
adjunct  professor  of  patholog}'  and  clinical  medicine,  was  already  studying 
assiduously  with  the  microscope  the  pathological  changes  in  the  kidneys  in 
Bright's  disease  and  still  other  morbid  processes,  as  viewed  indeed  from  the 
standpoint  of  the  new  cellular  pathology  just  struggling  into  the  light.  But 
of  opportunity  for  the  student  himself  to  acquire  even  the  rudiments  of  the 
technique  of  the  microscopic  study  of  the  organs  and  tissues  in  health  and 
disease,  there  was  none.  It  was  not,  therefore,  just  at  this  juncture  in 
Welch's  history  that  his  interest  in  pathology  asserted  itself. 

A  compelling  circumstance  was,  however,  imminent.  Among  the  prizes 
offered  to  students  was  one  provided  by  Doctor  Seguin,  then  the  professor 
of  diseases  of  the  nervous  system,  for  the  best  report  of  his  clinical  and 
didactic  lectures.  It  consisted  of  a  Varick  microscope  fitted  with  superior 
French  triplex  lenses.  This  prize  was  won  by  Welch,  and  it  proved  indeed 
to  be  the  spark  which  ignited  the  tinder  of  his  latent  interest  in  pathology 
and  caused  it  to  burst  into  flame.  Fortunately  Welch  now  entered  in  October, 
1874,  upon  his  interneship  at  Bellevue  Hospital,  where  this  strongly  aroused 
impulse  was  to  find  an  abundant  field  for  expression.  He  now  also  came 
more  directly  under  Delafield's  influence,  and  was  thrown  with  the  elder 
Janeway.  Much  of  his  time  was  spent  in  the  deadhouse  performing  autopsies, 
first  on  his  own  and  then  on  many  other  cases;  and  it  is  a  remarkable  tribute 
to  his  technical  skill  and  acumen  of  observation,  as  well  as  felicity  of 
description,  that  Delafield  invited  him  to  use  his  special  book  for  recording 
the  protocols  of  the  postmortem  examinations,  and  that  he  was  made  a 
curator  of  the  Wood  Museum  attached  to  the  Hospital. 

Although  it  was  perhaps  not  clearly  perceptible  at  the  time,  it  now 
appears  that  the  circumstances  surrounding  and  thus  acting  upon  the  sensi- 
tive imagination  of  Welch,  the  student,  were  favorable  to  his  development; 
for  notwithstanding  the  poverty  of  material  resources  and  of  laboratory 
facilities  of  the  era,  he  had  the  good  fortune  to  come  under  the  influence  in 
the  medical  college  of  not  a  few  men  of  remarkable  mental  vigor  and  attain- 
ments. Besides  tiiose  already  mentioned,  there  were  on  the  faculty  of  the 
College  in  his  day  Dalton  and  Curtis  in  physiology,  St.  John  and  Chandler 
in  chemistry,  Edward  Curtis  in  materia  medica,  Markoe  in  surger}%  Sands 
and  Sabine  in  anatomy  and  McLane  in  obstetrics;  weekly  clinical  lectures 


INTEODUCTION  xv 

were  given  by  Willard  Parker  and  T.  Gaillard  Thomas,  the  prestige  of  whose 
strong  personalities  and  eminent  careers  in  surgery  and  in  obstetrics  and 
gynecology  respectively  must  have  been  potent  forces.  He  was  thrown  as 
prosector  into  close  association  with  Sabine  and  with  the  demonstrators  of 
anatomy,  John  Curtis  and  McBurney.  It  was  especially  at  the  suggestion  of 
Sabine  that  Welch  wrote  his  graduating  thesis  upon  goitre,  which  received  the 
first  prize,  and  in  the  preparation  of  which  he  familiarized  himself  with 
medical  literature  and  bibliography  at  the  ISTew  York  Hospital  Library. 
At  Bellevue  Hospital  his  contacts  with  Delafield  and  with  Janeway  became 
numerous  and  close,  the  forerunner,  as  it  chanced,  of  a  relationship  destined 
to  become  even  more  intimate  and  significant  at  a  somewhat  later  period. 

Moreover,  the  era  in  which  the  young  student  found  himself  was  one  of 
fundamental  flux  of  belief  brought  about  by  the  new  cellular  pathology  and 
the  discoveries  of  Pasteur  just  impending.  Into  this  whirlpool  of  shifting 
ideas,  which  were  to  move  in  the  next  succeeding  years  with  ever-increasing 
speed,  Welch  with  his  eager,  open  and  responsive  mind  was  thrown.  That 
his  imagination  was  powerfully  stirred  by  the  intellectual  ferment  of  the 
time  may  be  assumed.  One  circumstance  is,  however,  quite  clear :  at  this  stage 
pathology  as  an  independent  career  had  not  been  seriously  before  his  mind, 
nor  was  it  so  to  present  itself  until  a  whole  new  set  of  experiences  had  been 
passed  through. 

The  year  and  a  half's  interneship  over,  Welch  is  about  to  take  ship  for  what 
proved  to  be  for  him  and  us  a  great  adventure.  In  April,  1876,  in  company 
with  his  friend  and  fellow  townsman.  Dr.  Frederic  S.  Dennis,  he  sailed 
on  the  Cunarder  "  Bothnia  "  for  Liverpool.  From  Liverpool  he  went  to 
London  where  he  spent  a  few  days,  crossed  the  channel  from  Harwich  to 
Eotterdam  and  made  his  way  leisurely  along  the  flowering  Dutch  and  Belgian 
fields  as  the  spring  was  passing  into  the  mild  early  summer  months,  toward 
Strassburg,  the  first  stopping  place  on  the  long  but  important  road  which 
was  about  to  fascinate  his  view. 

Welch's  European  experience  begins  with  Waldeyer,  the  Director  of  the 
Anatomical  Institute  in  Strassburg,  with  whom  he  studied  normal  histology. 
This  subject  was  of  course  taken  up  on  account  of  its  fundamental  importance 
as  a  basis  for  pathological  histology.  But  it  is  significant  that  the  interest 
in  chemistry,  also  as  a  foundation  subject,  which  carried  Welch  to  New  Haven 
on  the  very  threshold  of  entrance  to  his  medical  studies,  had  remained  alive ; 
hence  part  of  his  time  was  spent  in  Hoppe-Seyler's  laboratory,  under  the 
master  himself  and  his  assistant  Baumann,  in  working  through  the  former's 
well-known  textbook  in  physiological  chemistry.  In  addition,  time  was 
found  to  attend  von  Eecklinghausen's  autopsies  and  demonstration  course, 
although  at  this  period  no  further  courses  were  taken  with  this  master  of 


XVI 


IXTRODUCTION 


pathology  and  for  the  reason  that  Welch  concluded  that  until  a  grounding 
in  normal  histology  was  secured,  it  would  not  be  profitable  to  pursue  patho- 
logical histology. 

The  summer  semester  at  an  end,  Welch  left  Strassburg  for  Leipzig,  the 
summer  vacation  being  spent  with  a  friend  in  a  pedestrian  tour  in  Switzer- 
land and  northern  Italy.  It  is  of  interest  to  inquire  just  what  was  the  lure 
of  Leipzig.  Obviously  Waldeyer  was  the  attraction  in  Strassburg;  now 
it  was  Ileubner  and  Wagner  who  drew  the  student  to  Leipzig.  At  that 
time  Heubner  had  not  entered  the  field  of  pediatrics  in  which  he  afterwards 
became  celebrated,  but  he  was  working  rather  in  the  field  of  neurology ;  and, 
indeed,  it  was  his  important  book  on  the  diseases  of  the  blood  vessels  of  the 
brain,'  which  Welch  had  read,  that  determined  the  choice.  If  we  undertake 
to  penetrate  further  into  the  source  of  Heubner's  attraction  for  Welch,  we 
are  led  back  to  the  days  at  the  College  of  Physicians  and  Surgeons  in  New 
York  and  the  lectures  of  Seguin  which  had  exerted  a  strong  influence  on 
Welch,  so  that  if  we  had  then  inquired  whither  he  was  tending  in  medical 
specialization  we  should  have  discovered  that  he  was  looking  to  diseases  of 
tiie  nervous  system  as  the  field  for  practice,  while  pathology  remained  his 
main  interest  and  subject  of  training  in  Germany,  although  he  could  not 
then  anticipate  its  pursuit  as  a  means  of  livelihood  on  his  return  to  America. 

Circumstances  were,  however,  to  defeat  this  consciously  worked  out  pro- 
gram. In  due  course  Welch  subscribed  for  Heubner^s  course,  only  to  find 
very  quickly  that  the  latter  was  not  then  interested  in  teaching;  soon  the 
course  began  to  languish  and  the  students  to  absent  themselves,  and  it  was 
not  long  until  Welch  was  looking  elsewhere  to  fill  his  time.  Wagner,  who 
later  succeeded  Wunderlich  in  the  chair  of  internal  medicine,  was  at  the  time 
professor  of  pathological  anatomy.  Welch  found  Wagner's  courses  and  the 
opportunities  afforded  for  independent  work  by  his  institute  admirably 
adapted  for  his  own  purpose.  Here  he  attended  autopsies  and  obtained  speci- 
mens of  tissue  for  microscopic  examination.  At  first  the  blocks  were  given  as 
a  favor ;  but  later  Wagner's  interest  having  become  aroused  he  would  person- 
ally select  the  specimens  for  examination  and  for  report.  In  this  manner 
Welch  occupied  his  mornings;  the  afternoons  were,  however,  still  free.  He 
attended  Wagner's  polyclinic,  which  kept  him  in  touch  with  practical 
medicine. 

At  this  period  Ludwig's  laboratory  was  the  centre  of  attraction  for  the 
talented  men  in  Germany  and  also  for  many  foreigners  especially  interested 
in  physiology,  Welch  decided  to  offer  himself  and  was  accepted  by  Ludwig. 
That  the  choice  was  a  propitious  one  is  shown  by  the  group  of  men  at  that 
time  working  with  Ludwig  and  with  whom  Welch  was  now  associated.    The 

•  Heubner.    Die  luetlsche  Erkrankungen  der  Hirnarterien,  Leipzig,  1874. 


INTEODUCTION  xvii 

first  assistant  was  the  gifted  and  inspiring  Kronecker  with  whom  Welch 
formed  an  enduring  friendship.  Among  foreign  students  was  Pawlow,  and 
Drechsel  and  Flechsig  were  in  charge  of  the  chemical  and  the  histological 
divisions  of  Ludwig's  laboratory.  Welch  was  set  by  Ludwig  to  study  the 
gangha  and  nerves  of  the  auricular  septum  of  the  frog's  heart  with  the 
gold  chloride  impregnation  method,  in  the  course  of  which  he  actually 
brought  into  view  the  ganglionic  cells  with  T-shaped  fibres  which  Eanvier 
described  in  detail  somewhat  later.  The  semester  closed  and  the  usual 
"Ahschied"  supper  was  given  by  Kronecker.  Of  course  Welch  was  invited 
and  there  was  characteristically  exhibited  a  model  of  the  ganglion  cell  with 
fibres  both  entering  and  leaving  it — a  novel  and  as  we  now  know  a  histo- 
logically highly  important  event. 

The  first  year  of  Welch's  European  study  was  now  over.  It  had  been 
spent  in  preparing  himself  in  normal  histology,  physiological  chemistry, 
pathological  anatomy  and  physiology ;  and  it  may  be  asked  to  what  purpose 
and  for  what  ultimate  end  ?  The  answer  is,  in  order  to  be  ready  to  study 
with  Virchow,  whose  institute  he  had  visited  during  a  short  stay  in  Berlin. 
This  expectation  was  indeed  the  force  back  of  the  concentration  on  normal 
liistology,  the  reason  for  embracing  eagerly  a  histological  problem  from 
Ludwig,  the  motive  in  following  Wagner's  autopsy  and  microscopic  courses ; 
and,  after  all,  the  wish  was  to  be  frustrated  and  Welch's  activities  were  to  be 
directed  along  a  wholly  new  direction  and  into  fresh  channels. 

The  new  impulse  came  from  Ludwig  who  did  not  share  the  enthusiasm, 
at  least  in  the  overwhelming  degree  then  current,  for  the  cellular  patholog}' 
of  the  period.  Perhaps  this  response  was  the  less  hearty  because  he  did  not 
have  the  strong  sense,  as  so  many  seemed  to  have,  of  a  great  innovation,  but 
rather  viewed  Virchow^s  doctrines  as  the  extension,  perhaps  even  the  consum- 
mation, of  the  earlier  conceptions  and  discoveries  of  Schwann,  Schleiden, 
Picmak  and  Eeichert;  or  possibly  it  was  his  physiological  bias  or  even  a 
subtler  appreciation  of  the  impending  influence  of  the  study  of  function  on 
the  growth  of  pathology,  which  led  him  to  induce  Welch  to  alter  his  plans  and 
to  offer  himself  to  the  brilliant  young  pathologist  Cohnheim  to  whom  he 
undertook  to  write  urging  him  to  receive  Welch  and  to  furnish  him  with 
a  rewarding  (lohnendes)  theme. 

This  choice  proved  highly  fortunate.  As  one  reviews  Welch's  own  pub- 
lished work,  his  immediate  influence  on  his  students,  or  the  more  general 
effect  which  his  career  has  had  on  medical  education,  it  is  now  quite  obvious 
that  his  intellectual  temper  was  of  the  order  called  dynamic,  and  his  vigorous 
responses  were  to  concepts  built  on  facts  of  function  far  more  than  of  form 
and  structure.  The  summer  semester  of  1877  with  Cohnheim  in  Breslau 
was  perhaps  the  most  delightful  and  satisfying  of  all  the  time  Welch  spent 


xviii  INTRODUCTION 

abroad ;  and  fortunately  we  possess  a  pen  picture  of  him  at  that  particular 
time,  drawn  in  clear  and  sympathetic  lines. 

Salomonsen,  afterwards  professor  of  pathology  at  Copenhagen  and  the 
present  Xestor  of  medicine  in  Denmark,  had  also  come  to  Breslau  for  the 
summer  semester.  The  two  foreign  students,  the  first  foreigners  who  studied 
with  Cohnheim,  were  at  once  thrown  together;  there  existed,  indeed,  that 
subtle  quality  in  the  temperaments  of  the  two  men  that  quickly  made  for 
close  association  and  then  intimate  friendship — a  rare  relation  which  neither 
distance  nor  fleeting  years  have  severed.  Salomonsen  states  that  the  two 
men  who  most  influenced  his  own  life  were  Carl  Weigert  and  William  H. 
Welch.  He  goes  on  to  enlarge  and  say  that  he  and  Welch  had  many  points 
of  contact:  both  were  sons  of  physicians,  both  on  return  to  their  o^vn  coun- 
tries hoped  to  become  pathologists  to  municipal  hospitals,  and  both  regarded 
it  as  a  matter  of  course  that  anyone  wishing  to  enter  on  the  career  of 
pathologist  should  aspire  to  work  under  Colmheim. 

The  two  foreigners  were  proud  of  the  distinction — what  two  eager  young 
men  would  not  be? — of  being  the  only  foreigners  in  the  laboratory  among 
such  present  or  prospective  stars  as  Weigert,  Ehrlich,  Lassar,  Lichtheim, 
Albert  Neisser,  Senftleben  and  0.  Eosenbach.  They  were  always  together — 
from  early  morning  to  late  afternoon — and  they  were  taken  up  cordially 
by  their  German  colleagues  of  whose  intimate  circle  they  made  a  part.  I 
venture  to  quote  a  particularly  appropriate  paragraph  from  Salomonsen: 

"  That  by  accident  I  should  have  found  so  gifted  a  man  and  investigator 
as  Welch  in  Breslau,  I  at  that  time  as  well  as  later,  regarded  as  the  greatest 
good  luck.  Cohnheim  knew  well  how  to  appreciate  Welch,  and  he  recom- 
mended him  for  the  professorship  of  pathology  at  the  Johns  Hopkins  Uni- 
versity where  Welch  exerted  a  profound  influence  on  the  development  of 
medical  education  in  the  United  States,  and  where  the  present  generation 
of  American  pathologists  calls  him  master." 

It  was  in  this  remarkable  atmosphere  that  Welch  spent  a  precious  semester. 
The  work  of  the  laboratory  was  pretty  sharply  divided  between  the  autopsies 
conducted  mostly  by  Weigert,  and  the  experimental  investigations  in  which 
Cohnheim  shone  ever  brighter  and  brighter.  The  particular  problem  which 
Cohnheim  assigned  to  Welch  was  the  ascertaining  of  the  origin  of  acute 
general  oedema  of  the  lungs.  This  is  perhaps  not  the  place  to  go  into 
minutiae  of  tiiat  splendidly  conceived  and  executed  piece  of  experimental 
work.  It  was  in  many  ways  fortunate  that  Cohnheim  was  too  preoccupied 
at  the  time  reflecting  on  his  theory  of  tumors  and  in  the  preparation  of  his 
textbook  on  general  pathology  to  do  more  than  propose  the  problem  which 
Welch  developed  largely  according  to  his  own  notions  of  logical  sequence. 
Cohnheim,  indeed,  was  greatly  surprised  when  contrary  to  his  preconception 


INTEODUCTION  xix 

of  the  process,  Welch  found  the  factors  involved  in  it  to  be  mechanical. 
The  masterly  paper  describing  this  piece  of  work  as  it  appears  in  Vir chows 
Arcliiv  was  written  out  by  Welch  in  German  and  printed  quite  as  he  prepared 
it.  Cohnheim  seems  not  to  have  altered  essentially  the  composition,  the 
mode  of  presentation  or  the  conclusions  arrivfed  at.  Unfortunately  for  future 
controversy  Cohnheim  misconstrued  the  implications  of  Welch's  experiments 
and  in  his  epochal  Lectures  on  General  Pathology  he  substituted  for  the 
term  disproportion  (Missverhaltniss)  employed  by  Welch  to  express  the 
disharmony  (often  caused  by  spasm)  in  action  of  the  two  cardiac  ventricles, 
the  term  paralysis  (Ldhmung) ,  which  implies  only  one  form  of  disharmony. 

The  by-products  of  this  semester  on  Welch's  development  were  as  impor- 
tant as  the  direct  influences.  Salomonsen's  studies  on  tuberculosis  of  the 
eye  initiated  him  into  the  experimental  side  of  the  tuberculosis  problem. 
Salomonsen  relates  an  incident  showing  the  great  impression  made  upon 
the  two  foreign  students  by  the  first  example  of  generalized  tuberculosis  in 
the  guinea  pig  which  they  observed.  Their  enthusiasm  evoked  hearty  laugh- 
ter from  Cohnheim.  It  was,  moreover,  the  period  of  Heidenhain's  early  brilli- 
ant work,  of  the  rich  harvest  of  Cohn,  the  botanist;  and  to  cap  the  climax,  the 
occasion  of  Koch's  visit  to  Breslau  to  lay  before  Cohnheim  and  Cohn  the 
facts  of  his  studies  on  anthrax,  in  the  demonstration  of  which  all  the  workers 
in  Cohnheim's  laboratory  were  permitted  to  share.  Finally,  Weigert  with 
Ehrlich  was  just  applying  the  aniline  dyes  to  the  staining  of  tissue  elements 
and  bacteria  and  had  recently  completed  his  study  of  smallpox,  in  the  course 
of  which  he  demonstrated  by  staining  methods  the  masses  of  micrococci 
within  the  pustules.  Ehrlich  also,  although  not  yet  graduated,  was  literally 
dabbling  in  the  aniline  stains  and  it  was  a  common  event  to  see  him  with 
hands  covered  up  to  the  wrists  with  dyes  of  many  colors.  The  close  friend- 
ship of  Welch  with  Weigert  and  Ehrlich  dates  from  this  period. 

It  is  significant  that  the  spirit  of  the  Institute  was  favorable  to  the  new 
bacteriology  and  that  Cohnheim  and  his  associates  were  all  looking  to  the 
new  science  to  unlock  doors  still  concealing  the  origin  of  the  diseases  called 
infectious — an  attitude  striking  in  its  difference  from  the  skeptical  and 
rather  disdainful  one  of  the  Virchow  school  of  pathology.  Thus  on  leaving 
Breslau,  Cohnheim  sent  Welch  to  Vienna  by  way  of  Prague,  in  order  that  he 
might  visit  Klebs  who  was  engaged  in  the  study  of  acute  endocarditis  from 
the  microbiological  side.  There  he  spent  several  stimulating  days,  during 
which  Klebs  showed  him  through  his  excellent  museum  and  demonstrated  his 
preparations  showing  microorganisms  (micrococci)  in  the  ulcerative  lesions 
of  acute  endocarditis.  The  impression  which  Klebs  made  upon  Welch  was 
very  strong;  and  in  the  light  of  present  knowledge,  the  accuracy  and  presci- 


IX  INTEODUCTION 

ence  of  Klebs'  work,  well  in  advance  of  his  period,  not  only  on  endocarditis 
but  on  diphtheria  and  experimental  syphilis  as  well,  have  become  clearly 
apparent. 

The  next  stop  in  the  educational  journey  was  made  at  Vienna  which  was 
still  a  kind  of  Mecca  for  foreign  medical  students  of  all  nationalities.  The 
immediate  objective  was  a  place  in  Strieker's  laboratory,  in  order  to  continue 
his  studies  in  experimental  pathology.  As  an  index  of  the  high  feelings 
prevailing  at  the  time  it  may  be  mentioned  that  once  Strieker  learned  that 
Welch  had  been  with  the  heterodox  Cohnheim  who  taught  that  the  pus  cell 
was  merely  an  emigrated  leukocyte,  he  was  not  inclined  to  receive  him  as 
a  worker  in  his  laboratory.  One  purpose  of  the  visit  to  Vienna  was  to  study 
embr\-ology  under  Schenck,  but  the  choice  was  not  fortunate  and  Schenck  was 
soon  forsaken.  It  is  interesting  to  note  that  Welch  and  Prudden  found 
themselves  together  in  Vienna  in  their  search  for  an  opportunity  to  study 
embryology. 

On  the  whole,  the  chief  lure  of  Vienna  for  the  pathologist  was  its  almost 
inexhaustible  store  of  pathological  anatomical  material.  The  reign  of 
Rokitansky  was  over,  and  his  successor  was  Heschl,  the  discoverer  of  the 
methyl-violet  reaction  for  amyloid,  but  a  far  less  significant  personality. 
The  greater  attraction  was  the  young  Chiari  who  was  teaching  and  working 
with  the  vigor  which  afterwards  became  so  notable  and  carried  him  by  way  of 
Prague  to  Strassburg  to  succeed  the  eminent  von  Recklinghausen.  To  him 
Welch  went,  but  not  to  spend  his  entire  time.  There  survived  in  his  mind, 
it  appears,  a  residue  of  distrust  that  pathology  would  after  all  afford  him  a 
career  in  America,  or  was  it  the  love  still  for  the  more  immediately  practical 
aspects  of  medicine  which  led  him  to  enter  upon  courses  on  the  skin  under 
Hebra,  on  neurology  and  psychiatry  under  Meynert,  on  the  eye,  and  other 
special  subjects?  But  Vienna  meant  for  Welch  much  more  than  gross 
pathology  and  the  medical  specialties.  The  great  city  with  its  splendid 
museums  of  art,  its  grand  opera  and  its  vivid  life  introduced  features  of 
another  order  into  his  experience,  feeding  that  general  culture  in  literature, 
history,  and  the  fine  arts  which  came  to  distinguish  him  quite  as  much  as 
his  many-sided  medical  attainments,  Welch  remained  in  Vienna  until  the 
Christmas  holidays,  when  he  turned  his  steps  for  a  second  time  toward 
Strassburg,  spending  a  few  days  en  route  in  Wiirzburg  with  Rindfleisch  and 
his  assistant  Ziegler. 

The  second  pilgrimage  to  Strassburg  was  the  carrying  out  of  a  plan  formed 
by  Welch  at  the  outset  of  his  European  study.  He  recognized  in  von  Reck- 
linghausen the  outstanding  representative  of  the  Virchow  school  of  patholo- 
gists, and  Iiis  attendance  upon  the  autopsies  at  the  Pathological  Institute, 
while  he  was  a  pupil  of  Waldeyer,  had  stimulated  his  zeal  to  work  directly 


INTRODUCTION"  xxi 

under  the  master.  This  desire  could  not  be  at  once  appeased,  for  as  we  have 
seen,  Welch  lacked  the  preparation  in  normal  histology  which  he  regarded 
as  essential.  But  now  that  this  requisite  was  supplied  and  the  work  with 
Ludwig  and  with  Cohnheim  had  provided  a  fair  foundation  for  further 
building,  Welch  offered  himself  to  von  Eecklinghausen  and  was  accepted. 
As  another  indication  of  the  commotion  which  Cohnheim's  investigations 
were  making  in  the  placid  waters  of  Virchowian  pathology,  it  may  be  cited 
that  once  von  Eecklinghausen  learned  Welch  was  fresh  from  the  laboratory 
of  that  heretical  pathologist,  he  chose  as  a  theme  for  his  special  study  the 
inflammation  of  the  cornea  of  the  frog  induced  by  various  caustic  chemicals. 
The  essential  point  of  difference  involved  in  the  contentions  of  the  Virchow 
and  the  Cohnheim  schools  related  to  the  origin  of  the  pus  cell.  Was  it  derived 
by  multiplication  from  the  fixed  tissue  cells,  or  was  it  a  leukocyte  emigrated 
from  the  blood  ?  The  controversy  has  long  been  settled  in  favor  of  the  latter, 
or  Cohnheim  view;  but  in  January,  1878,  and  for  many  years  thereafter  it 
raged  with  vigor  and  even  bitterness.  The  cornea  was  selected  because  of 
its  condition  of  non- vascularity.  The  novel  experimental  procedure  employed 
at  von  Eecklinghausen's  suggestion  by  Welch  was  the  excision  of  the  cornea 
after  the  injury  and  immersion  in  the  aqueous  humor  of  the  frog  or  bullock, 
and  observation  continued  over  long  hours  under  the  microscope.  That 
cells  moved  toward  the  injured  spot  in  the  non-vascular  specimen  was  shown 
beyond  peradventure  and  even  that  they  divided ;  what  was  simpler,  therefore, 
than  to  conclude  that  migration  is  not  dependent  on  the  presence  of  the 
blood,  and  hence  pus  cells  are  not  translated  leukocytes?  This  inference, 
however,  was  not  drawn  by  Welch,  who  recognized  that  the  reasoning  is 
fallacious.  The  fuU  explanation  of  the  observed  phenomena  waited  on  later 
studies  and  even  on  recent  discoveries.  We  now  know  that  connective  tissue 
cells,  among  which  the  corneal  corpuscles  and  the  cells  of  Descemet's  mem- 
brane are  classed,  are  motile;  and  as  cells  endowed  with  movement  they  are 
attracted  by  certain  stimuli  called  "  chemical,"  such  for  example  as  arise  in 
tissue  constituents  acted  on  by  chemicals  and  in  other  ways.  Moreover,  as 
we  now  know,  these  fixed  tissue  cells  readily  multiply  in  vitro,  and  thus  we 
arrive  at  the  conclusion  that  the  chemically  altered  spot  in  the  cornea  attracts 
towards  itself  neighboring  uninjured,  motile  corneal  and  other  cells,  that 
these  cells  aggregate  about  the  site  of  the  injury  and  even  multiply  there,  and 
thus  give  what  may  be  called  a  spurious  appearance  of  a  collection  of  pus 
cells.  For  it  should  be  remembered  that  we  are  dealing  with  a  period  in  which 
tissues  were  not  yet  being  stained  with  certain  nuclear  and  other  dyes  that 
bring  into  view  brilliant  and  subtle  distinctions  of  cellular  structure; 
but  that  the  "  inflamed  "  cornea  was  merely  silvered  in  order  that  the  cell 


xxii  INTRODUCTION 

outlines  might  become  perceptible,  and,  if  desired,  was  subsequently  stained 
with  haematoxyhn  to  show  the  nuclei. 

This  practice  of  putting  to  the  test  new  discoveries  and  contentions  even 
under  somewhat  hostile  circumstances  was  not  a  poor  discipline  for  the 
future  teacher  of  pathology  in  the  United  States.  The  experience  may 
indeed  be  regarded  as  having  brought  into  play  under  favoring  circumstances 
a  critical  faculty  inclined  perhaps  to  leniency,  while  it  held  up  as  it  were  to 
the  mirror  of  his  perceptions  in  a  somewhat  summary  fashion  the  facts  of  the 
ultimate  and  ineradicable  residue  of  personal  bias  in  all  men,  no  matter  how 
great.  In  the  long  future  years  during  which  Welch  dispensed  knowledge 
and,  what  is  rarer,  vtdsdom  at  The  Johns  Hopkins  University  and  elsewhere, 
he  came  as  near  as  it  is  perhaps  possible  for  a  mere  mortal  to  come,  in  escaping 
the  blemish  of  preconception  and  prejudice  and  in  preserving  and  presenting 
the  ideal  of  the  open  though  balanced  mind. 

But  it  would  be  wrong  to  infer  that  there  was  not  also  a  constructive  side 
to  this  period  with  von  Eecklinghausen.  The  pathologist  was  great  in 
attainments,  and  stimulating  as  a  teacher.  He  engaged  Welch  in  discussion 
of  many  topics  in  pathology  which  were  current  at  the  time.  One  of  these 
related  to  the  origin  of  tumors,  regarding  which  von  Reckhnghausen  was 
endeavoring  to  formulate  his  views  along  lines  which  have  since  become  more 
familiar.  He  inclined  to  the  conception  that  a  kind  of  fertilization,  whether 
by  conjugation  or  otherwise,  took  place  among  the  cells,  leading  to  the  uncon- 
strained multiplication  characteristic  of  cancer  and  other  tumors,  in  conse- 
quence of  which  irregularities  of  division  arose  that  were  the  striking  obvious 
signs  of  the  cellular  abnormality.  Welch  always  retained  an  admiration  for 
von  Recklinghausen  as  a  great  pathological  anatomist. 

The  first  European  adventure  was  now  approaching  its  conclusion  and 
was  to  receive  a  suitable  ending  by  a  first  visit  to  Paris  and  a  second  to 
London.  It  is  far  simpler  and  more  satisfying  perhaps  to  leave  to  the 
imagination  the  picture  of  Welch  in  the  great  and  beautiful  French  city 
with  its  wealth  of  present  interests  and  of  historic  backgrounds  everywhere 
insistent.  The  fact  may,  however,  be  mentioned  that  time  was  found  during 
the  two  or  three  weeks  of  his  stay  to  hear  Ranvier,  whom  he  admired  greatly 
and  whose  book  on  histology  had  been  his  guide,  and  to  visit  the  main 
hospitals.  In  Txindon  he  heard  Lister  lecture  at  Kings  College  Hospital, 
and  shared  in  the  prevailing  excitement  which  arose  from  Lister's  daring 
surgical  exploit  of  opening  the  knee  joint.  The  next  was  the  final  act,  namely 
taking  ship  at  Liverpool  for  the  United  States. 

The  arrival  in  New  York  in  the  spring  of  1878  brought  forward  a  question 
which  could  be  permitted  to  remain  in  the  background  in  Europe,  but  now 


INTEODUCTION  xxiii 

must  be  answered.  Undoubtedly  Welch  possessed  wares  garnered  at  home 
and  abroad — but  to  what  market  were  they  to  be  taken  ?  That  the  practice 
of  medicine  would  be  a  necessary  corollary  to  any  other  ambition  he  might 
indulge,  seemed  never  to  have  been  doubted  by  him.  Where  else  were  the 
necessary  pecuniary  rewards  to  come  from?  There  seemed  no  alternative 
but  to  decide  immediately  whether  he  should  choose  ISTew  York  or  Norfolk 
as  a  field  of  operations.  In  Norfolk  his  father  was  still  busily,  if  not  very 
remuneratively,  engaged  in  country  practice,  in  the  course  of  which  he 
dispensed  much  kindness  and,  according  to  tradition,  worldly  wisdom  with 
his  medicines.  It  strikes  one  now  as  very  odd  that  Welch  should  have  hesi- 
tated at  this  juncture  in  his  choice  of  New  York  or  of  Norfolk.  The  anomaly 
can  best  perhaps  be  explained  by  taking  into  account  his  remarkable  modesty. 
It  seems  almost  impossible  of  belief  that  one  so  gifted  and  innately  so  force- 
ful should  not  be  aware  in  some  degree  of  the  part  which  nature  had  cast 
for  him.  But  whatever  pangs  of  indecision  he  may  have  suffered  were  about 
to  be  allayed  by  destiny  in  the  form  of  Doctor  Goldthwaite. 

Success  in  attaining  interneships  in  hospital  or  appointments  to  the 
medical  services  of  the  Army  and  Navy  was  still  determined  by  the  results 
of  competitive  examination.  To  meet  this  situation  the  private  "  quiz  "  had 
arisen  and  operated  about  the  medical  schools  and  upon  the  aspiring  medical 
students.  The  practice  has  now  been  generally  discredited  and  discontinued ; 
but  in  1878  and  for  many  years  afterwards  the  "  quiz  "  if  successful  was 
a  reputable  and  a  relatively  highly  remunerative  affair.  The  "  quiz  "  masters 
adapted  the  cramming  process  to  the  peculiarities  and  foibles  of  the  indi- 
vidual examiners,  which  they  sedulously  set  themselves  to  learn.  It  is  now 
obvious  that  on  joining  Goldthwaite's  "  quiz  "  Welch  never  regarded  the 
undertaking  as  more  than  a  stop-gap.  It  should  not  now  surprise  us  to  learu 
that  the  combination  of  Goldthwaite  and  Welch  proved  irresistible  and  soou 
outdistanced  all  competitors ;  it  could  choose  the  most  promising  students  and 
its  product  gained  the  prize  interneships.  Welch  endured  the  "  quiz  "  three 
years,  after  which  and  while  it  was  at  the  height  of  its  popularity  he  with- 
drew. The  reason  is  sufficiently  apparent  now,  but  then  with  the  system  in- 
trenched as  it  were,  it  required  insight  and  force  to  convict  it  of  its  salient 
defect,  namely  that  of  being  a  bad  method,  viewed  from  the  standpoint 
of  educational  discipline. 

The  "  quiz  "  was,  after  all,  merely  an  incident,  the  main  import  of  which 
was  that  it  ensured  the  necessary  income,  while  leaving  much  of  Welch's 
time  for  more  engrossing  pursuits.  As  a  matter  of  fact,  Welch  had  offered 
himself  for  practice  and  occupied  at  this  period  rooms  with  his  friend  Dennis 
at  21  East  Twenty-first  Street,  adjacent  to  the  office  of  his  old  teacher,  Alonzo 


xxiv  INTEODUCTION 

Clark,  who  would  refer  occasional  patients  to  the  young  men.  The  volume 
of  Welch's  practice  never  became  embarrassing,  so  that  he  was  still  free  to 
follow  his  major  bent,  which  was  to  teach  pathology. 

The  outlook  for  pathology  in  New  York  in  1878  was  not  bright.  The 
extent  and  the  nature  of  the  teaching  had  not  changed  materially  since  Welch 
was  a  student  in  the  medical  college.  New  York  was  as  much  cut  off  from 
the  strong  currents  moving  in  Germany  and  France  along  the  three  main  lines 
of  pathology — pathological  anatomy,  experimental  pathology  and  bacteri- 
olog)' — as  if  Europe  and  America  were  not  connected  by  a  common  intel- 
lectual bond.  Welch  was,  indeed,  destined  to  play  the  principal  part  in  break- 
ing the  barrier  of  American  isolation,  but  at  this  time  when  he  was  offered 
by  Dr.  Francis  Delafield  the  lectures  on  pathology  during  the  summer 
semester  at  the  College  of  Physicians  and  Surgeons,  he  declined  the  oppor- 
tunity, because  it  carried  with  it  no  chance  to  set  up  a  laboratory,  which  was 
the  one  essential  of  Welch's  aspiration.  But  what  was  denied  him  at  the 
College  of  Physicians  and  Surgeons,  was  about  to  be  put  before  him  at 
Bellevue  Hospital  Medical  College.  This  rival  institution  proposed  to  build 
two  small  rooms  over  a  hallway,  which,  added  to  another  room,  Welch  could 
turn  into  a  laboratory. 

The  invitation  was  accepted  at  once,  and  Welch  made  his  first  break  with 
the  established  traditions  in  New  York.  For  this  was  the  heyday  of  schism 
in  medical  schools  and  feelings  ran  high  among  the  several  faculties,  and 
the  position  of  his  alma  mater,  the  "  P.  and  S.,"  in  the  medical  hierarchy  of 
the  time  was  regarded  as  supreme.  Certain  of  Welch's  friends  were  not  happy 
over  his  choice  and  even  considered  that  he  had  made  "  the  mistake  of  his 
life."  Perhaps  there  were  disadvantages  of  a  kind  in  a  Bellevue  connection 
as  contrasted  with  the  far  greater  prominence  of  the  "  P.  and  S."  establish- 
ment, but  whatever  they  may  have  been  in  general,  they  were  more  than 
compensated  for  by  the  laboratory  and  its  proximity  to  the  deadhouse  at 
Bellevue.  The  new  pathological  laboratory  became  at  once  an  influential 
factor  in  the  medical  educational  system  of  New  York,  and  students  came 
there  to  Welch  from  all  three  medical  schools. 

The  leaven  worked  rapidly,  for  very  soon  the  College  of  Physicians  and 
Surgeons  awoke  to  the  growing  demands  of  pathology.  A  part  of  the 
faculty  had  not  ceased  to  view  Welch's  defection  regretfully,  and  now  that 
the  Alumni  Association  proposed  to  set  up,  under  Delafield's  general  direc- 
tion, a  pathological  laboratory,  its  direct  conduct  was  offered  to  Welch. 
The  invitation  was  not  accepted,  but  in  declining  it  Welch  characteristically, 
as  we  should  now  say,  put  in  another  strong  stroke  for  pathology,  as  the 


INTEODUCTION  xxv 

following  letter,  which  also  explains  his  sense  of  obligation  to  the  BeUevue 
College,  illustrates: 

"  New  York,  October  9,  1878. 
"  My  dear  Doctor  Prudden  : 

"  A  few  days  ago  Professor  Delafield  told  me  of  the  following  scheme  which 
the  Twenty-third  Street  Medical  College  has  on  foot.  A  laboratory  for 
histology  and  pathology  is  to  be  established  in  connection  with  the  college, 
by  means  of  a  fund  given  for  the  purpose  by  the  alumni.  It  is  to  be  taken 
hold  of  in  an  earnest  way,  for  the  laboratory  is  to  hold  the  same  relation 
to  the  college  as  the  dissecting  room  does;  that  is,  each  student  will  be 
obliged  during  some  part  of  his  course  to  work  there  before  he  can  take  his 
degree.  Doctor  Delafield  proposed  that  I  should  go  in  as  his  first  assistant 
and  have  charge  of  the  histological  department,  and  assist  him  as  much  as 
necessary  in  the  pathological  part.  The  salary  was  to  be  five  hundred  dollars 
for  the  first  year,  and  I  believe  more  subsequently.  I  was  naturally  delighted 
with  the  offer  and  thought  it  to  be  just  what  I  wanted,  an  opportunity  to 
work  in  the  direction  where  I  had  studied  most.  Upon  speaking  of  the 
matter,  before  coming  to  a  decision,  with  some  of  the  professors  at  Bellevue, 
I  find  that  they  are  reluctant  to  have  me  leave  there,  and  even  represent  it 
as  not  the  square  thing  for  me  to  go  at  present.  The  latter  motive  especially 
has  influenced  me  to  stay,  as  I  do  not  believe  it  pays  to  do  anything  unfair. 
I  feel  as  if  I  were  relinquishing  a  great  opportunity  and  do  not  see  any  equiva- 
lent for  it  at  present  at  Bellevue,  but  as  there  is  a  feeling  there  that  it  would 
not  be  right  for  me  to  leave,  I  am  going  to  stay  and  have  so  told  Doctor  Dela- 
field. He  asked  me  if  I  knew  anyone  who  would  be  competent  for  the  posi- 
tion, saying  there  are  a  great  many  in  New  York  who  think  they  are,  but  few 
who  really  are. 

"  I  immediately  suggested  your  name  and  he  at  once  seemed  pleased,  and 
deputed  me  to  hunt  you  up  by  a  letter  and  communicate  the  proposal  to  you. 
I  really  think  the  offer  an  advantageous  one,  in  fact  presenting  an  oppor- 
tunity better  than  any  other  I  know  for  one  with  the  tastes  and  resolution 
which  you  have  formed.  I  do  not  know  anyone  who  could  do  greater  justice 
to  the  work  there  than  yourself,  and  it  seems  to  me  to  present  great  possi- 
bilities for  the  future.  Personally  I  should  like  to  have  you  here  in  New 
York,  for  I  fear  I  am  going  to  rust  out  unless  I  have  someone  to  talk  witli 
and  help  me  on  concerning  the  subject  in  which  we  are  both  interested. 

"  I  do  not  know  whether  this  letter  will  even  reach  you.  Will  you  at  least 
drop  me  a  postal  card  when  you  receive  it,  for  if  I  do  not  hear  from  you  in 
a  day  or  two,  I  am  going  to  resort  to  further  means  of  hunting  you  up.  I 
should  also  like  to  know  how  you  decide." 

With  Prudden's  installation  at  the  College  of  Physicians  and  Surgeons, 
pathology  had  come  to  be  recognized  as  a  subject  of  independent  merit  and 
proportions,  to  be  taught  practically,  by  two  of  the  leading  medical  schools 
of  the  country.  Prudden  was  a  pupil  of  Arnold  of  Heidelberg,  under  whom 
he  had  mastered  a  precise  and  delicate  pathological  histological  technique; 
and  later  at  A^ienna,  in  part  alongside  Welch,  he  had  imbibed  the  essence  of 


xxvi  INTEODUCTION 

the  teaching  of  morbid  anatomy.  Thus  and  at  last  in  the  persons  of  Welch 
and  Pnidden,  American  pathology  had  come  to  be  united  with  the  best 
sources  of  its  inspiration  abroad;  and  from  now  on  the  main  task  was  to 
widen  and  diversify  tliis  stream  in  the  accomplishment  of  which  purpose 
Welch's  career  stands  forth  preeminent. 

Welch  was  now  fairly  launched  on  a  career  in  pathology,  but  his  struggles 
were  not  all  over.  The  serious  question  all  along  was  the  economic  one. 
Pathology  was  not  a  remunerative  profession  at  the  time.  The  fees  from 
students  taking  the  course  were  small,  the  occasional  windfall  from  a  private 
autopsy  was  precarious.  There  were,  of  course,  the  fees  for  the  examination 
of  specimens  for  physicians  and  surgeons,  and  the  possibility  existed  then  as 
now  of  turning  this  practice  into  considerable  income.  But  Welch  shrank 
from  an  enterprise  which  would  consume  his  time  and  yield  no  corresponding 
scientific  return.  After  the  abandonment  of  the  "  quiz ''  a  way  out  was  found 
in  that  he  became  first,  assistant  demonstrator  and  later  demonstrator  of 
anatomy  at  Bellevue,  both  paid  positions;  and  then  he  offered  himself  for 
practice.  That  his  neighbor  and  teacher,  Alonzo  Clark,  sent  him  patients, 
we  have  seen;  it  remains,  however,  to  add  that  the  now  elderly  gentleman 
formed  the  habit  of  referring  his  surgical  cases  to  Welch. 

This  was  also  the  period  of  Welch's  association  with  the  elder  Flint, 
then  at  the  zenith  of  his  prominent  career  as  teacher  and  consultant.  He 
was  professor  of  medicine  and  the  leading  spirit  at  the  Bellevue  College, 
and  a  great  social  and  professional  figure  in  New  York.  Flint  was  engaged 
at  the  time  in  bringing  out  a  new  edition  of  his  Practice  of  Medicine  and 
asked  Welch  to  revise  the  sections  on  pathology.  Welch  "jumped  at  the 
chance  "  and  was  given  a  free  hand,  except  for  two  or  three  topics  which  were 
reserved  for  his  son,  Austin  Flint,  Jr.  Anyone  today  reading  Flint's 
Practice  of  Medicine  will  recognize  the  superior  merit  of  the  introductory 
chapters  on  general  pathology  and  the  sections  on  the  pathology  of  the 
special  diseases  there  given,  the  whole  amounting  to  a  textbook  on  pathology. 

It  was  Flint's  habit  to  precede  his  lectures  on  "  practice  "  with  a  sketch  of 
the  pathology  of  the  subject  to  be  presented.  Pretty  soon  these  preliminary 
lectures  were  turned  over  to  Welch,  who  lost  apparently  no  opportunity 
to  increase  the  prestige  of  pathology  in  the  curriculum.  Thus  he  introduced 
the  class  autopsy,  which  he  held  once  a  week  in  a  room  filled  with  students. 
Notwithstanding  these  clear  indications  of  Welch's  unmistakable  bent 
and  trend,  Flint  assumed  all  along  that  Welch  would  become  a  consultant 
and  succeed  him  in  the  professorship  of  medicine.  Indeed,  he  took  steps 
by  having  the  faculty  elect  Welch  to  the  clinical  professorship  of  medicine 
to  make  his  succession  certain.  Welch  on  learning  of  this  action  brought 
about  its  revocation,  first  because  of  the  injustice  which  he  considered  done 


INTRODUCTION"  xxvii 

to  the  then  incumbent  of  the  clinical  professorship,  and  next  because  of 
his  great  interest  in  pathology. 

Looking  backward  it  can  be  perceived  that  these  many  shifts  and  activities 
were  incidental  to  the  laboratory  of  pathology.  First  the  "  quiz/'  second  the 
demonstratorship  in  anatomy,  third  practice — each  in  turn  supplied  the 
necessary  income  in  money  to  cover  living  expenses.  Each  in  turn  was  fol- 
lowed with  energy  and  success,  and  abandoned  as  soon  as  the  needed  income 
w^as  available  from  a  source  less  exacting  of  the  precious  time  to  devote  to 
autopsies  and  laboratory,  or  freer  from  considerations  violating  fundamental 
beliefs  in  sound  educational  method.  Pretty  soon  his  skill  in  performing 
autopsies  and  his  eagerness  for  pathological  material  brought  to  Welch  privi- 
leges from  the  Babies'  Hospital  and  also  from  the  coroner,  with  whom  Welch 
stipulated  that  he  was  not  to  testify  in  court.  It  is  of  passing  interest  to 
note  that  none  of  these  were  paid  positions,  but  that  at  this  time  a  small 
stipend  came  to  Welch  from  the  registrarship  of  the  Woman's  Hospital, 
which  position  he  then  held,  and  where  he  made  the  autopsies  and  studied 
the  specimens,  mainly  ovarian  tumors,  removed  at  operations. 

Half  a  dozen  years  had  passed  since  his  return  from  the  European  studies, 
and  Welch  had  intrenched  himself  deeply  in  the  medical  life  of  New  York. 
He  was  the  outstanding  pathologist  and  representative  of  the  new  pathology, 
and  there  came  to  him  to  study  or  to  work,  the  alert  and  ambitious  among 
the  medical  students  and  young  practitioners  of  the  day.  These  years  had 
contained  not  a  little  that  was  pleasant,  but  much  also  that  was  discouraging 
to  one  who  possessed  a  deeper  feeling  for  and  a  wider  outlook  on  medical 
education.  It  is  true  that  improvements  were  creeping  into  the  medical 
curriculum ;  the  annual  sessions  at  this  time  were  indeed  extended  from  five 
to  seven  months  and  more  emphasis  was  being  placed  on  the  laboratory  and 
less  on  the  purely  didactic  form  of  instruction;  but  progress  was  painfully 
slow  and  medical  teaching  lagged  sadly  behind  that  of  continental  schools. 
However,  a  turn  in  medical  affairs  was  impending  which  was  to  transform 
within  a  few  years  the  entire  educational  structure. 

The  Johns  Hopkins  Hospital  was  approaching  completion  and  the  thoughts 
of  President  Oilman  and  the  boards  of  trustees  of  The  Johns  Hopkins  Uni- 
versity and  Hospital  were  turning  toward  the  establishment  of  the  medical 
school  provided  for  in  the  splendid  gift  of  Johns  Hopkins.  A  leader  to 
guide  the  new  enterprise  was  sought,  and  it  is  quite  clear  from  Salomonsen's 
statement  that  President  Oilman  asked  Cohnheim's  advice,  and  doubtless  the 
advice  of  others  at  home  and  abroad.  Welch  seems  to  have  been  the  unani- 
mous first  choice.  Dr.  John  S.  Billings,  so  intimately  associated  with  the 
planning  of  the  Hospital,  visited  Welch  at  Bellevue,  doubtless  in  this  con- 
nection, and  Welch  was  invited  to  become  professor  of  pathology  in  the 
3 


xxviii  INTEODUCTION 

Universit}'  and  pathologist  to  the  Hospital.  The  great  opportunity  for  which 
he  had  waited  and  labored  and  toward  which  his  dearest  aspirations  turned 
had  now  come  to  Welch. 

There  was  no  doubt  in  Welch's  mind  that  the  Baltimore  venture  was 
full  of  promise  and  should  be  embraced.  In  the  meantime,  however,  his 
position  in  New  York  had  become  so  important,  it  is  not  surprising  that  a 
strong  effort  should  be  made  to  retain  him.  At  first  Welch's  friends  failed 
to  see  how  anyone  could  exchange  the  professional  opportunities  of  New 
York  for  those  of  provincial  Baltimore.  The  incidents  of  the  transition  from 
the  "  P.  and  S."  to  Bellevue  College  were  recalled  in  this  almost  grotesque 
adventure.  But  there  was  no  doubting  Welch's  seriousness,  and  hence  steps 
were  taken  at  once  to  thwart  his  plans.  The  fear  of  losing  Welch  was  the 
immediate  incentive  which  brought  the  Carnegie  Laboratory  into  being. 
Doctor  Dennis,  an  intimate  friend  and  admirer  of  Welch,  obtained  a  sum 
of  $50,000  from  Mr.  Carnegie  for  the  erection  of  the  laboratory.  But  there 
is  reason  to  believe  that  Doctor  Dennis  had  in  mind,  besides  the  purpose  of 
anchoring  Welch  to  New  York,  the  setting  up  of  the  laboratory  as  an  integral 
part  of  the  medical  educational  system  of  the  United  States. 

But  the  Carnegie  Laboratory  was,  after  all,  a  building  only,  with  such 
simple  and  necessary  equipment  as  was  demanded  by  the  work  of  the  period 
in  pathological  anatomy  and  in  bacteriolog}%  just  at  its  beginnings  in  the 
United  States.  There  was  no  provision  made  for  a  paid  staff,  and  there  were 
no  funds  for  daily  running  expenses.  Just  what  might  have  happened  had 
these  essentials  been  provided,  it  is  impossible  to  say,  for  undoubtedly  with 
the  erection  of  the  Carnegie  Laboratory  the  outlook  for  pathology  in  New 
York  had  suddenly  brightened.  But  the  vista  opened  before  Welch's  eyes 
at  Baltimore  was  extremely  fascinating,  and  strong  as  now  may  have  been 
the  motive  to  remain  in  New  York,  the  unprecedented  position  which  The 
Johns  Hopkins  University,  at  the  zenith  of  its  great  reputation,  had  attained 
in  fostering  science,  was  a  lure  not  to  be  resisted.  Everything  about  the 
opportunity  at  Baltimore  attracted  Welch,  who  wished  above  all  to  be  free 
to  develop  pathology  in  a  manner  approaching  that  which  he  had  come  to 
know  in  Germany;  and  fortmiately  for  the  history  of  medical  progress  in  the 
United  States,  he  yielded  to  manifest  destiny,  although  .in  doing  so  he  was 
breaking  with  old  and  devoted  friendships  and  turning  his  back  on  a  posi- 
tion in  New  York  never  yet  attained  by  a  devotee  of  a  laboratory  branch  of 
medical  science. 

In  the  six  years  which  had  elapsed  since  Welch  had  returned  from  his 
first  period  of  foreign  study,  the  center  of  interest  had  begun  to  shift  from 
the  purely  cellular  pathology  of  Virchow  to  that  of  the  microbiology  of 
Pasteur  and  Koch,  in  which  the  bacteria  appear  as  the  direct  incitants  of 


INTRODUCTION  xxix 

disease.  Here  at  last,  it  seemed,  were  to  be  discovered  the  agencies  whose 
actions  are  the  immediate  excitants  of  those  organic  and  cellular  changes  or 
lesions  constituting  the  visible  reactions  of  the  tissues  to  the  injurious  in- 
fluences taking  place  in  the  course  of  the  phenomenal  process  designated 
disease.  This  new  direction  of  development  was  highly  sympathetic  to 
Welch  who  had  been  a  spectator  at  Breslau,  at  the  prologue  to  this  swiftly 
moving  drama,  when  Koch  visited  Cohn  and  Cohnheim  in  order  to  exhibit 
his  anthrax  cultures.  Welch  desired  first-hand  knowledge  of  and  experience 
in  the  new  field,  and  as  The  Johns  Hopkins  Hospital  was  still  in  process  of 
construction,  we  find  him  setting  out  again,  in  the  summer  of  1884,  for 
Germany. 

The  new  goal  was  Koch  in  Berlin.  But  an  interview  with  him  at  the 
Eeichsgesundheitsamt  led  Welch  on  Koch's  advice  to  go  to  Munich  for  the 
autumn  to  study  under  Frobenius  in  Bollinger's  laboratory,  preparatory  to 
work  under  the  master  at  a  later  date.  It  appears  that  Koch  was  soon  to  leave 
the  Gesundheitsamt  to  be  established  in  the  Hygienic  Institute  under  imi- 
versity  auspices,  near  the  Alexanderplatz.  Frobenius  proved  a  slavish 
teacher  of  Koch's  technique,  which  he  communicated  to  his  pupils  along  with 
such  comments  as  he  had  gleaned  from  conversations  with  Koch.  Still,  it  was 
a  beginning  in  the  new  field,  and  the  relatively  unfavorable  conditions  led 
again,  as  once  before  at  Leipzig,  to  connections  of  great  future  importance. 
Here  Welch  made  the  acquaintance  of  Hans  Buchner  and  also  of  Escherich, 
Lehmann,  Neumann,  Celli  and  others  who  had  come  to  follow  the  first  course 
in  bacteriology  given  in  a  university.  Especially  with  Celli,  who  had  already 
begun  his  studies  of  the  malarial  parasite,  he  formed  an  intimate  and  endur- 
ing friendship.  Welch  followed  at  this  time  Kitt's  demonstrations  in  animal 
pathology  in  the  veterinary  school  and  worked  in  von  Pettenkofer's  institute 
of  hygiene  vsdth  the  master  himself  and  his  assistant,  Eenk.  All  was  grist 
that  came  to  Welch's  mill  for  in  after  years  the  former  experience  was  to 
bear  fruit  in  his  important  studies  on  the  swine  diseases  and  the  close  interest 
in  Theobald  Smith's  work,  and  the  latter  to  contribute  to  that  comprehensive 
grasp  of  the  subject  of  hygiene  now  being  embodied  in  the  new  school  of 
public  health  at  Baltimore,  his  latest  and  highly  remarkable  creation. 

Welch  did  not  go  at  once  from  Munich  to  Berlin  but  acting  still  under 
Koch's  direction  went  in  January  to  Gottingen  to  work  under  Fliigge,  who 
was  professor  of  hygiene  and  much  closer  to  Koch  and  being  advised  by 
him.  This  period  was  in  every  way  advantageous,  as  Flugge  was  a  far  more 
inspiring  and  systematic  teacher  than  Frobenius,  and  his  influence  proved 
lasting  and  valuable.  Here  again  he  became  acquainted  with  fellow  students 
gathered  in  Gottingen  for  the  same  purpose,  who  afterward  became  dis- 
tinguished bacteriologists,  such  as  MacFadyen,  Nicolaier  and  Wyssokowitch. 


XXX  INTEODUCTION 

The  final  touch  in  Welch's  preparation  in  the  new  bacteriology  was  ad- 
ministered by  Koch  himself — a  vivid  teacher — who  himself  conducted  the 
courses,  which  he  had  previously  organized  for  military  doctors  and  which  had 
such  far-reaching  consequences.  Fortune  again  threw  Welch  and  Prudden 
together,  for  the  latter  who  had  taken  over  the  laboratory  at  the  College  of 
Physicians  and  Surgeons  established  by  the  Alumni  Association,  was  now 
in  Berlin  also  seeking  training  in  the  new  science  of  bacteriology.  The  course, 
which  was  of  a  few  weeks'  duration,  consisted  essentially  in  the  practice  of 
isolating  bacterial  species  by  means  of  Koch's  solid  culture  technique  or 
by  passage  of  them  through  the  animal  body,  in  order  to  effect  separation  of 
virulent  from  other  varieties,  and  in  the  consideration  of  form,  staining 
reactions  and  physiological  and  pathogenic  propensities.  The  climax  of  the 
course  was  the  study  of  the  bacillus  inducing  Asiatic  cholera.  At  this  period 
not  a  little  apprehension  existed  that  Europe  might  again  be  visited  by  that 
scourge.  The  disease  had  raged  in  India  and  Egypt  and  the  year  before 
had  gained  a  foothold  in  Europe  in  certain  Mediterranean  ports — hence  the 
desirability  of  mobilizing  a  small  army  of  trained  bacteriologists  to  combat 
that  plague  should  it  threaten  in  earnest.  Koch  himself  was  deeply  im- 
pressed with  the  danger;  indeed  so  appalling  did  he  consider  the  calamity 
of  an  epidemic  outbreak  of  cholera  in  Europe  that  he  did  not  trust  himself 
to  bring  with  liim  to  Berlin  cultures  of  the  bacillus  isolated  in  India  or 
Egypt,  but  preferred  to  destroy  them  lest  by  inadvertence  they  should  gain 
access  to  food  or  water.  Now,  however,  that  cholera  actually  existed  on 
European  soil  and  danger  of  its  spread  was  imminent,  the  circumstances 
not  only  justified  but  compelled  instruction  in  its  bacteriological  detection, 
and  for  this  purpose  he  went  to  Toulon  to  secure  anew  fresh  cultures. 

But  Koch  admonished  his  pupils  not  to  carry  away  from  the  laboratory 
living  cultures  of  the  cholera  bacillus.  This  piece  of  sound  advice,  following 
the  end  of  the  course  at  a  Kneipe  held  in  honor  of  the  Geheimrath  led  to 
an  amusing  incident.  The  next  morning  Welch  and  Prudden  met  acci- 
dentally at  an  early  hour  on  one  of  the  bridges  spanning  the  Spree,  each, 
as  it  seems,  seeking  secrecy.  It  developed  that  each  had  gone  to  an  apothe- 
cary's shop  and  purchased  concentrated  sulphuric  acid  (or  was  it  a  saturated 
solution  of  corrosive  sublimate?),  wliich  they  had  poured  over  the  surface 
of  tube  cultures  of  the  cholera  bacillus  originally  intended  to  be  taken  with 
them  to  America  and  that  they  now  proceeded  to  drop  into  the  Spree.  They 
expected,  of  course,  to  see  the  tubes  sink  immediately  out  of  sight,  instead 
of  which  they  had  the  momentar}-^  disquieting  experience  of  observing  them 
'  bobbing  up  and  down  as  they  slowly  floated  down  stream.  The  guilty  pair 
hurried  away,  just,  it  is  said,  as  a  large  Schutzmann  appeared  on  the  scene. 


INTEODUCTION  xxxi 

An  impression  of  Koch  and  the  influence  of  his  instruction  at  the  time 
is  given  by  Prudden: 

"  Thus  the  course  in  the  study  of  bacteria,  of  one  month's  duration,  in 
Koch's  laboratory  was  brought  to  an  end,  and  the  writer  cannot  refrain  from 
remarking  that  the  calm,  judicial  mind  of  Doctor  Koch — the  master  worker 
in  his  field — his  marvelous  skill  and  patience  as  an  experimenter,  his  wide 
range  of  knowledge  and  his  modest,  unassuming  presentation  of  his  views 
are  all  calculated  to  inspire  confidence  in  the  results  of  his  own  work,  to 
stimulate  his  students  to  personal  exertion  in  this  field,  and  to  lend  certainty 
to  the  already  wide-spread  hope  that  ere  long  through  the  resources  of  science 
we  shall  be  able  to  cope  successfully  with  those  most  terrible  and  fatal  enemies 
of  the  human  race — the  acute  infectious  diseases."  ^ 

Welch  arrived  in  Baltimore  in  September,  1885,  and  there  found  Council- 
man at  work  in  pathology.  He  immediately  joined  Welch  and  together  they 
set  up  a  laboratory  in  a  couple  of  rooms  on  the  top  floor  of  the  biological 
laboratory,  offered  them  by  ISTewell  Martin.  The  two-storied  building  at 
the  Hospital,  designed  as  a  deadhouse,  was  hurriedly  completed  and  con- 
verted into  a  pathological  laboratory.  This  arrangement  was  intended 
merely  as  a  stop-gap  in  the  emergency  and  until  the  buildings  for  the  medical 
school,  then  expected  soon  to  be  organized  and  constructed,  could  be  provided. 
As  it  happened,  the  consummation  of  the  medical  school  project  was  long 
delayed  and  the  small  quarters  intended  merely  for  a  deadhouse  and  its 
essential  adjuncts,  became  the  permanent  home  of  the  pathological  depart- 
ment, as  well  as  indeed  the  actual  physical  foundation  on  which  were  later 
erected  two  additional  stories  to  house  temporarily  the  departments  of 
anatomy  and  pharmacology  of  the  medical  school.  When  in  a  few  years  those 
two  departments  secured  elsewhere  other  and  more  adequate  quarters,  the 
pathological  department  spread  through  all  the  vacated  space,  which,  in 
view  of  its  expanding  activities,  was  sorely  needed. 

The  history  of  the  pathological  department  of  The  Johns  Hopkins  Uni- 
versity and  Hospital,  that  was  to  play  so  profound  a  part  in  the  educational 
progress  of  the  United  States,  dates  from  1886  at  which  time  Welch  began 
to  exert  the  influence  which  peculiarly  distinguishes  his  career  from  that 
of  his  predecessors  in  this  country  and  elsewhere.  Hitherto  there  had  been 
abroad  departments  or  institutes  of  pathology  by  which  was  usually  meant 
pathological  anatomy  and  histology,  and  sometimes  experimental  pathology' 
or  bacteriology,  Welch's  receptive  and  constructive  mind  responded  power- 
fully to  the  training  he  received  in  these  several  branches  of  science,  so 
that  he  became  master  not  of  one  branch  only,  but  of  all.    Thus  it  came  about 

'  Prudden,  T.  M.,  on  Koch's  method  of  studying  bacteria.  Report  to  the  Con- 
necticut State  Board  of  Health  for  1885,  pages  225-226. 


xxxii  INTRODUCTION 

that  in  setting  up  the  pathological  department  in  Baltimore  he  inevitably, 
and  doubtless  unconsciously,  employed  all  these  resources  of  knowledge  and 
progress,  and  in  so  doing  inaugurated  a  new  era.  Hereafter  pathology,  at 
least  in  the  United  States,  could  hope  to  develop  symmetrically,  utilizing  for 
its  advancement  the  materials  and  methods  not  of  one  branch  of  the  science 
merely  but  of  all  branches,  main  and  collateral,  which  being  directed  toward 
it  might  suffice  to  render  a  pathological  phenomenon  more  comprehensible 
or  afford  the  solution  of  a  problem  in  medicine  otherwise  elusive. 

The  purpose  when  Welch  was  called  to  Baltimore  was  to  proceed  immedi- 
ately with  the  selection  not  only  of  the  staff  for  The  Johns  Hopkins  Hospital 
but  of  the  faculty  of  the  medical  school  as  well.  Unforeseen  economic  con- 
ditions postponed  the  realization  of  the  latter  design;  but  as  the  hospital's 
resources  had  not  been  reduced  by  the  unhappy  accident  which  crippled  the 
finances  of  the  University,  a  clinical  faculty  was  brought  together.  Welch's 
part  in  the  choosing  in  1888  and  1889  of  Doctors  Osier,  Halsted,  and  Kelly 
was  conspicuous  and  decisive,  just  as  later  with  the  opening  of  the  medical 
school  in  1893  it  was  his  acquaintance  with  their  work  and  his  unerring 
judgment  of  them  as  men  which  added  to  the  distinguished  trio  Doctors 
Mall,  Howell,  and  Abel  in  the  completion  of  the  first  major  faculty  of  The 
Johns  Hopkins  Medical  School.  But  Welch  did  not  await  the  opening  of  the 
hospital  or  the  consummation  of  the  plan  for  a  medical  school  to  start  active 
teaching  and  to  get  under  way  problems  of  research.  Work  was  begun  in  an 
informal  manner  with  medical  graduates  and  advanced  students  in  biology, 
and  the  quality  of  the  material  and  the  effects  of  Welch's  influence  can  be 
gathered  from  the  list  of  names  of  the  first  group  to  assemble  under  him. 
In  it  were  Councilman,  Mall,  Nuttall,  Abbott,  and  Bolton.  Before  long  this 
informal  plan  was  superseded  by  systematic  courses  in  pathology,  including 
pathological  histology  and  bacteriology,  and  university  lectures.  These  were 
not  permitted,  however,  to  degenerate  merely  into  short,  superficial  series 
of  demonstrations,  lectures  and  exercises ;  but  they  always  carried  with  them 
the  freshness  of  the  unexpected  from  the  wide  variety  of  activities  going  on 
in  the  laboratory  and  also  the  incentive  to  individual  endeavor  when  any  new 
point  arose  exciting  to  someone's  curiosity. 

With  the  founding  of  the  medical  school  along  the  lines  now  familiar 
but  none  the  less  at  that  time  novel  to  the  point  of  revolution,  the  break  with 
the  past  was  complete  and  the  aspiration  which  for  so  long  kept  Welch  a 
student  and  a  teacher  was  to  be  realized,  and  in  full  measure.  Henceforth 
medical  education  in  the  United  States  was  to  be  on  a  basis  equalling  at  least 
the  best  continental  model.  Tlie  faculty  of  the  medical  school  was  to  lose  its 
local  and  provincial  character  and  to  be  representative  of  the  most  potent 
forces  in  the  country,  while  the  young  men  and  women  seeking  to  enter 


INTRODUCTION  xxxiii 

medicine  were  to  possess  a  foimdation  training  in  physical,  chemical  and 
biological  science  and  to  be  equipped  so  as  to  follow  in  the  original  tongues 
the  greater  scientific  medical  literatures  of  the  French  and  the  Germans. 
This  was  revolution  indeed;  but  like  all  of  Welch's  reforming  acts  it  was 
a  programme  of  construction  not  of  destruction.  Welch's  career  stands 
forth  supreme  as  a  force  for  advancement,  whether  in  research,  education, 
hospital  organization  or  public  health;  but  one  searches  in  vain  his  writings 
or  the  records  of  his  public  utterances  for  evidence  of  vehemence  or  denun- 
ciation. His  was  too  understanding  and  sympathetic  a  spirit  to  Judge  men 
and  things  harshly  for  faults  and  shortcomings,  the  origins  of  which  were 
sunk  deeply  into  a  past  whose  circumstances  were  so  unlike  those  of  the 
present.  He  made  use  rather  of  the  gentler  art  of  persuasion  by  exposition 
and  example,  leavening  now  here  and  now  there,  until  the  cumulative  power 
of  the  intellectual  and  social  ferment  induced  became  so  great  as  to  be 
irresistible,  and  the  whole  mass  was  moved  forward. 

From  the  outset  Welch  was  the  central  figure  and  guiding  genius  of  the 
medical  group.  The  pathological  laboratory  became  an  active  centre  of 
research  and  teaching.  Welch's  life  quickly  became  filled  to  overflowing. 
He  conducted  investigations  of  his  own,  launched  others  on  productive 
themes,  and  saw  to  it  that  the  invaluable  pathological  specimens  from  the 
surgeons  and  gynecologists  were  made  use  of  to  advance  knowledge  and 
train  a  generation  of  special  pathologists  in  those  important  fields.  He 
lectured  on  special  and  general  subjects  in  pathology  and  bacteriology  in 
a  manner  so  learned  and  fascinating  as  to  produce  impressions  not  only 
immediately  stimulating  to  his  auditors  in  high  degree  but  of  enduring 
permanence.  The  suggestiveness  of  these  lectures  led  frequently  to  new 
undertakings  in  research.  Moreover,  the  autopsies  he  performed,  his  demon- 
strations of  gross  pathological  specimens  and  his  teachings  at  the  microscope 
stand  out  as  unsurpassable  models.  He  entered  also  into  the  medical 
activities  of  Baltimore  and  of  the  State  of  Maryland,  and  became  a  great 
influence  for  betterment  in  private  and  public  medicine.  He  was,  of  course, 
the  first  dean  of  the  medical  school  and  guided  the  policy  of  the  new  institu- 
tion into  the  productive  channels  that  have  so  eminently  distinguished  it. 
His  many  talents  were  therefore  called  into  constant  play,  and  heavily  over- 
taxed as  they  must  often  have  been  there  was  never  indication  of  exhaustion. 
When  occasion  arose  he  was  always  ready,  eager  and  able  for  a  new  advance, 
as  witness  his  leading  part  in  the  recent  development  of  the  full-time 
system,  so-called,  in  the  clinical  branches  of  medical  teaching,  in  establishing 
a  model  school  of  public  health  and  hygiene,  and  in  serving  on  scientific 
and  philanthropic  boards  possessing  great  wealth,  for  promoting  scientific 


xxxiv  INTEODUCTION 

discovery  and  for  carrying  the  benefits  of  medical  knowledge  to  the  furthest 
parts  of  the  world. 

The  achievements  of  Welch  as  an  investigator,  teacher  and  reformer  in 
medicine  are  so  many  and  varied  that  it  is  not  possible  to  do  justice  to  them 
in  detail  in  a  mere  sketch.  This  is  particularly  true  of  that  part  of  his  career 
covered  by  the  Baltimore  and  Johns  Hopkins  period.  These  three  noble 
volumes  of  his  collected  papers  and  addresses  are  the  best  expression  of  his 
many-sided  activities.  And  yet  precious  as  they  are,  they  afford  no  real 
insight  into  Welch's  almost  flawless  personality,  the  depth  of  his  friendship 
and  wealth  of  his  kindness,  his  faculty  of  intense  application  and  devotion 
to  the  work  in  hand  whether  in  laboratory  or  in  public  interest,  his  com- 
manding influence  and  guiding  spirit  over  the  work  of  his  associates  and 
many  pupils,  the  stimulating  wholesomeness  of  his  public  activities,  and 
his  rarely  unselfish  and  tolerant  nature  which  led  him  to  shower  his  great 
gifts  prodigally  and  far  and  wide.  The  recipient  of  almost  every  honor 
in  the  gift  of  his  colleagues,  he  fortunately,  in  time,  saw  the  return  of  his 
labors,  increased  many-fold,  enriching  science  through  progress  made  in 
education,  in  deeds  performed  and  discoveries  by  the  men  and  institutions 
over  whose  destinies  he  had  presided.  And  lastly  these  volumes  fail  to 
show  us  still  another  side  of  Welch's  accomplishments  as  remarkable  almost 
as  those  of  the  science  we  so  love  to  laud  in  him.  I  refer  to  his  culture  outside 
the  realm  of  medicine  in  the  field  of  literature,  in  which  he  possesses  an 
almost  unerring  taste  for  the  best  in  poetry  and  prose,  and  in  the  domain 
of  the  fine  arts.  His  mind  is  indeed  stored  with  the  beautiful  creations  of 
other  men's  minds  from  ancient  times  to  our  own  day.  It  is  to  all  these 
remarkable  qualities,  innate  and  acquired,  united  in  one  man,  that  we  owe 
that  thrice  rare  personality  William  Henry  Welch,  master  in  medicine  and 
beloved  of  men. 

Simon  Flexxer. 


PATHOLOGY 


ZUR  PATHOLOGIE  DES  LUNGENODEMS ' 
(Aus  dem  pathologischen  Institut  in  Breslau) 

Obwohl  das  Lungeiiodem  der  haufigste  pathologische  Befund  am  Sections- 
tische  ist,  so  ist  es  doch  niemals  der  Gegenstand  einer  experimentellen 
Untersuchungsreihe  gewesen,  und  seit  L  a  e  n  n  e  c '  s  Beschreibungen  ^  ist 
unseren  Kenntnissen  iiber  diesen  haufigen  und  wichtigen  pathologischen 
Zustand  iiberhaupt  "Weniges  hinzugefiigt  warden.  Seit  der  Zeit,  in  welcher 
ein  Verhaltniss  zwischen  erhbhtem  Blutdruck  in  den  Capillaren  und  ver- 
mehrter  Ausscheidung  aus  denselben  vermuthet  worden  ist,  hat  man  ange- 
nommen,  dass  das  Hauptmoment  beim  Zustandekommen  von  Lungenodem 
in  einer  gesteigerten  Spannung  der  Lungencapillaren  zu  suchen  sei.  Da 
aber  die  Betrachtungen,  welche  dieses  Moment  zu  wiirdigen  versucht  haben, 
zum  grossten  Theile  ohne  Beriicksichtigung  der  Eigenthiimhchkeiten  des 
Lungenkreislaufs  oder  unter  irrthiimlichen  Yoraussetzungen  iiber  denselben 
gemacht  worden  sind,  so  habe  ich  nach  dem  Vorschlag  des  Herrn  Prof. 
Cohnheim  eine  Eeihe  von  Yersuchen  an  Kaninchen  und  Hunden  im 
Breslauer  pathologischen  Institute  angestellt,  welche  den  Zweck  hatten  mit 
Eiicksicht  auf  die  neueren  Forschungen  liber  den  Pulmonalkreislauf  unsere 
Kenntnisse  von  den  Ursachen  des  Lungenodems  zu  erweitern.  Meinem 
hochverehrten  Lehrer  spreche  ich  hiermit  fiir  seine  f reundliche  und  thatige 
Hiilfe  meinen  herzlichsten  Dank  aus, 

Xach  der  gangbaren  Anschauung  ist  das  Lungenodem  die  Folge  entweder 
einer  Hydramie  oder  einer  Hyperamie,  arterieller  oder  venoser. 

Was  das  hydramische  Oedem  betrifft,  so  haben  die  Yersuche  von  Cohn- 
heim und  Lichtheim*  ergeben,  dass  das  Lungenodem  nach  Infundi- 
rung  grosser  Mengen  von  Kochsalzlosung  zwar  bei  Kaninchen  kein  seltenes 
Ereigniss  ist,  doch  nicht  constant  eintritt,  und  bei  Hunden  selten  beobachtet 
wird.  Daraus  diirfen  wir  schliessen,  die  hydramische  Plethora  allein, 
obwohl  ein  begiinstigendes  Moment,  ist  nicht  im  Stande  Lungenodem  zu 
erzeugen,  sondem  das  Zustandekommen  desselben  erfordert  noch  einen 
zweiten  Factor.    TJeber  diesen  letzteren  werden  wir  spater  zu  handeln  haben. 

In  den  systematischen  Lehrbiichern  der  Medicin  werden  LungenhA'per- 
amie  imd  Lungenodem  gewohnlich  in  demselben  Capitel  und  ungetrennt 

^Arch.  f.  path.  Anat.  u.  Physiol,  u.  f.  klin.  Med.,  Berl.,  1878,  LXXII,  375-412. 
*Laennec,  De  I'auscultation  mediate.  T.  II.  Paris,  1819. 
=  Virchows  Archiv  Bd.  69.  S.  106. 

3 


4        ZUK  PATHOLOGIE  DES  LUNGENODEMS 

behandelt,  Darnach  kann  jede  Hyperamie,  seien  ihre  Natur  und  ihre 
TJrsachen  welche  sie  wollen,  wenn  sie  hochgradig  genug  ist,  Lungenodem 
zur  Folge  haben,  Des  Naheren  glaube  ich  die  gegenwartigen  Anschauungen 
am  richtigsten  darzulegen,  wenn  ich  die  Ansichten  iiber  Hyperamie  und 
Oedem  der  Lunge  wiedergebe,  welche  in  dem  Lehrbuch  von  Niemeyer* 
und  dem  Handbuch  der  Medicin  von  v.  Ziemssen''  enthalten  sind. 

Die  Hyperamie  der  Lunge  vsdrd  in  Fluxion  und  in  Blutstockuug  oder 
passive  Hyperamie  getheilt. 

Als  TJrsachen  einer  Fluxion  werden  von  Niemeyer  angef iihrt : 

1.  Gesteigerte  Herzaction, 

2.  Directe  Eeize,  wie  Einathmen  heisser  oder  mit  reizenden  Substanzen 
vermischter  Luft, 

3.  Collaterale  Hyperamie, 

4.  Verdiinnung  der  Luft  in  den  Alveolen  (verengerte  Glottis).  Diesen 
TJrsachen  f  iigt  Hertz  hinzu : 

5.  Wirkung  des  kalten  Trunks  bei  erhitztem  Korper  und  Abkiihlung  der 
Korperperipherie, 

6.  Entziindliche  Zustande. 

Als  TJrsachen  einer  Blutstockuug  werden  erwahnt : 

1.  Storung  des  Abflusses  des  Blutes  aus  den  Pulmonalvenen,  namentlich 
Stenose  und  Insufficienz  der  Mitralis  (seltener  Klappenaffectionen  der 
Aorta), 

2.  Jede  geschwachte  Herzaction. 

Bevor  wir  erwagen,  inwieweit  diese  verschiedenen  Momente  fahig  sind, 
Lungenodem  zu  verursachen,  werde  ich  zuerst  an  die  folgenden  wolilbekann- 
ten  Charaktere,  welche  dasselbe  darbietet,  erinnem,  Gewohnlich  tritt  das 
Lungenodem  plotzlich  auf  und  kann  fast  ebenso  rasch  verschwinden,  wie 
es  entstanden  ist;  es  ergreift  beide  Lungen;  es  erscheint  bei  den  verschieden- 
artigsten  Krankheiten  und  ist  ein  constanter  Begleiter  von  keiner;  es  tritt 
oftmals  bei  der  Agonie  auf,  eine  Begleiterscheinung  eher  als  eine  TJrsache 
des  Todes;  die  mikroskopische  TJntersuchung  einer  odematosen  Lunge 
zeigt  die  hochgradigste  Fiillung  der  Capillaren  und  zahlreiche  ausgetretene 
rothe  Blutkorperchen.  Von  dem  acut  auftretenden  allgemeinen 
Lungenodem,  wovon  hier  ausschliesslich  die  Eede  ist,  muss  dagegen  das 
serose  Transsudat  unterschieden  werden,  welches  sich  haufig  in  der  Nahe 
entziindeter  Lungentheile  befindet  und  gewohnlich  als  ein  collaterales  Oedem 
bezeichnet  wird. 

Wenden  wir  uns  also  zunachst  zu  einer  Kritik  der  verschiedenen,  oben 
angcgebenen  TJrsachen  des  Lungenodems! 

*Niemeyer,  Lehrb.  d.  spec.  Path.  u.  Therap.  Bd.  1.  Berlin,  1874. 
'Hertz,   Anamie   Hyperamie  und  Oedem   der   Lungen.     v.   Ziemssen's 
Handb.  der  spec.  Path.  u.  Therap.  Bd.  5.  Leipzig,  1874. 


ZUE  PATHOLOGIE  DES  LUNGENODEMS        5 

1.  Gesteigerte  Herzaction.  Wenn  wir  aus  den  Verhaltnissen 
im  grossen  Kreislauf  einen  Schluss  auf  den  Lungenkreislauf  ziehen  diirfen, 
dann  ist  es  von  vomherein  sehr  unwahrscheinlich,  dass  vermehrte  Blutzu- 
fuhr  (Fluxion)  zu  einer  Lunge,  welche  sich  nicht  in  entziindlichem  Zustande 
befindet,  und  aus  deren  Venen  der  Abfluss  nicht  gehindert  ist,  zu  Oedem 
fiihren  sollte.  Zu  anderen  Korpertheilen  kann  der  arterielle  Zufluss  be- 
trachtlich  vermehrt  werden,  zum  Beispiel  dureh  Erweiterung  der  zufiihren- 
den  Arterien  oder  durch  Verengerung  oder  Verlegung  anderer  Gefassgebiete, 
ohne  dass  eine  vermehrte  Abscheidung  aus  den  Capillaren  folgt.*  Es  soil  aber 
nach  Henle/  Niemeyer,  Hertz  u.  A.  ein besonderer  Grund  existiren, 
aus  welchem  bei  gesteigerter  Herzaction  das  Blut  sich  in  den  Lungen  haufen 
soil.  Dieser  von  vielen  Seiten  behauptete  Grund  ist  der,  dass  die  Lungen- 
capillaren  weniger  resistent  gegen  vermehrten  Bludruck  seien,  als  die 
Capillaren  anderer  Organe.  Dass  in  dieser  Beziehung  ein  absoluter  Unter- 
schied  existirt,  ist  kaum  zu  leugnen,  aber  Druck  und  Widerstande  im  Pul- 
monalkreislauf  sind  um  Vieles  geringer  als  im  Aortensystem,  und  es  ist  kein 
Grund  anzunehmen,  dass  im  Verhaltnisse  zu  d  i  e  s  e  m  Drucke  und  zu 
d  i  e  s  e  n  Widerstanden  die  Lungencapillaren  weniger  resistent  sind,  als 
andere  Capillaren.  In  diesem  Gebiete  aber,  auf  welchem  uns  die  meisten 
Factoren  unbekannt  sind,  ist  es  gef ahrlich  zu  speculiren  und  gliicklicher- 
weise  konnen  wir  auch  ohne  alle  Speculationen  auskommen.  Bei  jeder 
compensirten  hochgradigen  ]\Iitralstenose  muss  der  Druck  in  der  Pulnio- 
nalarterie  holier  sein,  als  ihn  ein  nicht  hypertrophisches  Herz  in  einer  Limge, 
in  der  keine  Hindernisse  fiir  den  Abiiuss  des  Blutes  existiren,  zu  Stande 
bringen  kann,  und  doch  giebt  es  in  diesem  Stadium  keine  Anzeichen,  dass 
die  „Eesistenz  der  Capillaren'^  iiberwunden  ist.  Dass  hier  keine  allmahlich 
sich  entwickelnde  Vermehrung  der  Widerstandsfahigkeit  der  Capillaren  in 
Betracht  zu  ziehen  ist,  beweist  der  Umstand,  dass  nach  einem  kiinstlich 
angelegten  Aorten-  oder  Mitralisf  ehler  der  Blutdruck  in  der  Arteria  carotis 
sich  nicht  andert.*  Die  Versuche  von  Lichtheim"  iiber  Unterbindung 
einer  Lungenarterie  sowohl,  wie  die  Versuche  liber  Unterbindung  der 
Lungenvenen,  welche  unten  berichtet  werden  sollen,  deuten  eher  auf  eine 
relativ  grossere  als  auf  eine  relativ  kleinere  Resistenz  der  Lungencapillaren 
im  Vergleich  mit  denen  anderer  Organe  hin.  Weder  physiologische  noch 
pathologische  Beobachtungen  sprechen  dafiir,  dass  erhohte  Herzkraft  allein, 
ohne  Hinzutreten  anderer  ]\Iomente,  in  den  Lungen  leichter  als  in  den 
iibrigen  Korpertheilen  Oedem  erzeugen  konne. 

*Emminghaus,  Arbeiten  aus.  d.  phys.  Anstalt  zu  Lieipzig.    1873.    S.  68. 
'  Handbuch  d.  rationellen  Pathologie.    Bd.  II.    S.  421.    Braunschweig,  1847. 
^Cohnheim,  Vorlesungen  iiber  allgemeine  Pathologie.    S.  38.    Berlin,  1877. 
"Lichtheim,  Die  Storungen  des  Lungenkreislaufs  und  ihr  Einfluss  auf  den 
Blutdruck.    Breslau,  1876. 


6        ZUE  PATHOLOGIE  DES  LUNGEXODEMS 

2.  DirecteEeize.  Diese  kormen,  insofem  sie  nicht  durch  Stonmg 
der  AthmiLDgsvorgange  oder  durch  ihre  Wirkuiig  auf  andere  Organe  todten, 
als  Entziindungserreger  fiir  die  Luftwege  und  die  Lungen  betrachtet 
warden."  L  a  s  s  a  r  "  beobaclitete  Lungenodem  als  eine  inconstante  Be- 
gleiterscheinung  des  Todes  in  Erstickungsfallen,  welche  ausnahnisweise  der 
Einathmung  von  Saurediimpfen  f olgen.  Die  Seltenheit,  mit  welcher  Lungen- 
odem nach  der  Einwirkung  von  directen  Eeizen  auf  die  Lunge  erscheint, 
macht  es  wahrseheinlieh,  da&s  es  nicht  der  unmittelbare  Effect  des  Eeizes 
sei,  sondem  denselben  Ursprung  hat,  wie  dasjenige  Oedem,  welches  bei  den 
verschiedensten  Todesarten  entsteht,  und  fiir  welches  ich  unten  versuchen 
werde,  eine  Erkliirung  zu  geben. 

3.  Collaterale  Hyperamie.  Gerade  bei  der  Lunge  hat  das 
sogenannte  collaterale  Oedem  eine  grosse  Eolle  gespielt.  Wenn  die  Circula- 
tion in  einem  Lungenlappen  oder  einer  ganzen  Lunge  gehemmt  -ward,  dann 
entwickelt  sich  in  den  freien  Theilen  eine  compensatorische  Hyperamie, 
welche  der  gangbaren  Anschauung  zufolge  zum  Oedem  fiihren  kann.  Als 
die  Folge  solcher  collateralen  Fluxion  fasst  Virchow"  das  Lungenodem 
auf,  welches  er  durch  Injection  von  Oel  in  die  Venen  erzeugte.  Die  Yer- 
suche  von  Lichtheim"  haben  uns  schon  gelehrt,  dass,  wenn  Aeste  der 
Lungenarterie  bis  zu  drei  Viertel  der  Arterienbahn  verlegt  werden,  der 
Druck  in  der  Arteria  carotis  keine  wesentliche  Veranderung  erleidet,  und 
der  Druck  in  den  offen  gebliebeuen  Arterien  der  Lunge  eine  gewisse  Steige- 
rung  zeigt,  welche  im  Verhaltnisse  zu  dem  normalen  niedrigen  Werthe 
desselben  steht.  Als  Folge  aber  dieser  seltcn  in  so  hohem  Grade  beim 
Menschen  zu  beobachtenden  collateralen  Hyperamie  hat  er  niemals  Lungen- 
odem gesehen,  und  auch  ich  war  nicht  im  Stande  ein  collaterales  Oedem  zu 
erzeugen.  Dass  in  den  Fallen,  in  welchen  ein  allgemeines  acutes  Oedem 
nach  embolischer  Yerstopfung  einer  Lungenarterie  entsteht,  dieses  auf 
anderen  Momenten  als  der  collateralen  Hyperamie  beruht,  beweisen  die  eben 
erwahnten  Yersuche  und  auch  die  Inconstanz  seines  Auftretens  uuter  diesen 
Umstiinden.  Der  haufige  Befund  von  Lungenembolien,  welche  ohne  jegliche 
symptomatische  oder  anatomische  Folgeerscheinung  entstanden  sind,  ist 
jedem  erfahrenen  Pathologen  bekannt. 

Wenn  aber  das  sogenannte  collaterale  Oedem  sich  nicht  auf  die  compen- 
satorische Hyperamie  zuriickfiihren  lasst,  woher  kommt  es  sonst?  Mit 
jenom  Xamen  werden  zwci  verschiedene  Zustiinde  bezeichnet,  einmal  das 
allgenieine  aout  auftretende  Oedem,  welches  bei  Krankheiten  entsteht,  die 

"  B.  H  e  i  d  e  n  h  a  i  n  .  Dieses  Archiv.  Bd.  70.  S.  441. 
"  Zeitschrift  fiir  pliys.  Chemie.  Bd.  I.  Hft.  3. 
"  Spec.  Path.  u.  Therap.   Bd.  I.   S.  191.   Erlangen,  1854. 
»  Op.  cit. 


ZUE  PATHOLOGIE  BES  LUNGENODEMS        7 

eine  Hemmung  der  Circulation  in  einem  Theile  der  Lunge  verursachen, 
fur's  zweite  die  locale  serose  Durchfeuchtung  des  Lungengewebes  in  der 
Nahe  von  entziindlichen  Heerden,  Neubildungen  u.  s.  w.  Der  erstere 
Zustand,  glaube  ich,  ist  denselben  noch  zu  besprechenden  Ursachen  zuzu- 
schreiben,  wie  das  allgemeine  Lungenodem  iiberhaupt,  der  letztere  dagegen 
als  ein  entziindliches  Oedem  aufzufassen.  Schwer  in  Einklang  zu  bringen 
mit  der  Hypothese,  dass  das  locale  collaterale  Oedem  die  Folge  bios  einer 
compensatorischen  Blutdrucksteigerung  sei,  ist  der  Umstand,  dass  die  Ver- 
breitung  desselben  oftmals  in  keinem  Verhaltnisse  zu  der  Grosse  der  Gefass- 
verengerung  steht.  Einerseits  sieht  man  haufig  um  kleine  lobulare  Pneu- 
monien,  kleine  embolische  Infarcte  u.  s.  w.  eine  verhaltnissmassig  grosse 
odematose  Zone,  andererseits  kann  man  dieselbe  ganzlich  vermissen  bei 
Krankheiten,  welche  grosse  Abschnitte  des  Lungenparenchyms  fiir  die  Cir- 
culation unwegsam  machen.  Wenn  einmal  eine  entziindliche  Gefassverander- 
ung  existirt,  dann  kann  bekanntlich  vermehrte  Blutzufuhr  zu  gesteigerter 
Transsudation  in  dem  betreffenden  Theile  flihren,"  und  deshalb  diirfen  wir 
nicht  einer  collateralen  Hyperamie  jeden  Einfluss  absprechen,  das  Haupt- 
moment  aber  ist  die  vorhergehende  Gefasswandveranderung.*° 

4.  Verdiinnung  der  Luft  in  den  Alveole n.  Vor  30 
Jahren  stellte  Mendelssohn"  eine  merkAviirdige  Theorie  auf ,  nach 
"welcher  das  Wesen  der  Lungenhyperamie  iiberhaupt  in  einer  Luftverdiin- 
nung  in  gewissen  Lungenpartien  zu  suchen  sei.  Er  ging  von  der  falschen 
Hypothese  aus,  dass  die  Veranderungen  der  Lunge  nach  Vagusdurchschnei- 
dung  auf  einer  Verdiinnung  der  Luft  in  den  Alveolen  beruhen.  „Diese  Luft 
verhalt  sich  zur  Schleimhaut  der  Lunge  wie  die  unter  einem  trockenen 
Schropfkopf ."  "  Die  Versuche  von  0.  Frey  *^  in  Betreff  der  Verengerung  der 
Trachea  sprechen  nicht  dafiir,  dass  eine  bedeutende  Lungenhyperamie  durch 
Hindemisse,  welche  den  Eintritt  der  Luft  in  die  Luftwege  beeintrachtigen, 
entstehe.  Eine  Verengerung  der  Glottis  als  eine  Ursache  des  Lungenodems 
zu  betrachten,  entbehrt  jedenfalls  der  experimentellen  und  der  klinischen 
Grundlage, 

5.  Wirkung  des  kalten  Trunks  und  Erkaltung  des 
K  o  r  p  e  r  s,     oder    allgemeiner    ausgedriickt,    Widerstande    im    grossen 

"  G  i  a  n  u  z  z  i ,  Berichte  d.  konigl.  sachsischen  Gesellschaft  der  Wissenschaften, 
1866.    Cohnheimu.  Lichtheim,!.  c.  S.  139. 

"Cohnlieim,  Vorles.  liber  allg.  Pathologie.  S.  261,  416,  419. 

^"Mendelssohn,  Der  Mechanismus  der  Respiration  und  Circulation,  oder 
das  explicirte  Wesen  der  Lungenhyperamie.    Berlin,  1845. 

"  Arch.  f.  phys.  Heilk.    1845.    S.  277. 

"  Die  pathologischen  Lungenveranderungen  nach  Lahmung  der  Nervi  vagi. 
Leipzig,  1877. 


8        ZUE  PATHOLOGIE  DES  LUNGENODEMS 

Kreislaufe  im  Allgemeinen.  Eine  Erklarung  fiir  die  Entstehung  der 
Lungenhyperamie  in  Folge  der  Wirkung  der  Kalte  auf  den  Magen  oder  auf 
die  Hautoberfliiche  hat  man  in  der  Thatsache  zu  finden  geglaubt,  dass  nach 
Yerengerung  ausgedehnter  Gefassgebiete  (Baucheingeweide,  Haut)  der  Blut- 
dmck  in  anderen  Theilen  des  Aortensystems  steijgt."^  Die  Versuehe  von 
Liclitheim  aber  haben  nachgewiesen,  dass  die  Spannung  im  kleinen 
Kreislauf  in  holiem  Grade  von  Druckveranderungen  des  grossen  Kreislaufs 
imabhangig  ist.  In  Uebereinstimmung  damit  finde  ich,  dass  beim  Hunde 
der  Pulmonaldruck  ohne  wesentliche  Veranderung  bleibt,  wenn  den  einzigen 
offenen  Weg  fiir  das  Blut  aus  dem  linken  Ventrikel  in  den  Korperkreislauf 
die  eine  Arteria  earotis  oder  die  eine  Subclavia  bildet.  Der  Dnick  in  der 
Carotis  kann  in  Folge  von  Hindernissen  in  der  Circulation  zu  mehr  als  dem 
Doppelten  seiner  normalen  Hohe  gebracht  werden,  ohne  dass  der  Pulmonal- 
duck  steigt.  In  Hinblick  auf  diese  Thatsache  diirfen  wir  nicht  eine 
Lungenhyperamie  in  Folge  von  Erkaltung  unmittelbar  von  einer  collateralen 
Blutdrucksteigerung  herleiten.  Die  Erkaltung  fiir  eine  Ursache  von  Hy- 
drops pulmommi  zu  halten,  entbehrt  iibrigens  der  klinischen  Berechtigung, 
und  in  den  seltenen  Fallen,  in  welchen  ein  Zusammenhang  vorhanden  zu 
sein  scheint,  sind  sicher  andere  Momente  im  Spiele. 

6.  EntziindlicheZustande.  Das  locale  collaterale  Lungenodem 
hat  Cohnheim  schon  mit  Eeclit  als  ein  entziindliches  angesprochen. 
Wirft  man  nun  die  Frage  auf,  ob  es  ein  primares,  idiopathisches,  entziind- 
liches Lungenodem  giebt,  so  liegt  kein  Grimd  vor,  ein  allgemeines  Lungen- 
odem entziindlicher  Xatur  anzunehmen.  Das  erste  Stadium  freilich  der 
Vaguspneumonie  und  das  der  crouposen  Pneumonie  haben  eine  grosse  Ver- 
wandtschaft  mit  localem  Lungenodem.'*'  Wenn  wir  aber  in  diesen  Fallen 
von  einem  entziindlichen  Lungenodem  sprechen  diirfen,  so  ist  damit  nur 
gemeint,  dass  in  Folge  einer  entziindlichen  Veranderung  der  Gefasswiinde 
ein  Zustand  entsteht,  welcher  die  grosste  Aehnlichkeit  mit  dem  Zustande 
der  Limgen  bei  gcAvohnlichem  Lungenodem  besitzt.  Dass  aber  das  Stauungs- 
und  das  entziindliche  Oedem  nicht  zu  identificiren  sind,  beweisen,  von  allem 
Andem  abgesehcn,  die  Untersuchungen  von  L  a  s  s  a  r  ^  iiber  die  Beschaffen- 
heit  der  Lymphe  bei  der  Entziindimg. 

Blutstockung.  Je  skeptischer  uns  unsere  Erf ahnmgen  iiber  das 
Zustandekommen  von  Wassersucht  im  grossen  Kreislaufe  hinsichtlich  der 

"Hermann  und  Ganz.Pfluger's  Archiv  fiir  Phys.  1870.   S.  8. 

""Frledlander,  Untersuchungen  iiber  die  Lungenentziindungen.  Berlin, 
1873. 

Unverriclit,  Studien  iiber  die  Lungenentziindung.  Inaug.-Dlss.  Breslau, 
1877. 

"Virchows  Archiv  Ed.  G9.  S.  516. 


ZUE  PATHOLOGIE  DES  LUNGENODEMS         9 

Moglichkeit  der  Entstehung  des  Lungenodems  durch  fliixionare  Hyperamie 
machen,  mit  desto  grosserer  Sicherheit  werden  wir  von  der  Blutstauung 
oder  venosen  Hyperamie  einen  derartigen  Effect  erwarten.  Weder  die 
anatomische  Structur  noch  die  physiologischen  Eigenschaften  der  Limgen- 
capillaren,  so  weit  sie  uns  bekannt,  gebeu  uns  Gruud  anzunehmen,  dass  sie 
nicht,  wie  andere  Capillaren,  eine  betrachtliche  Behinderung  des  Venen- 
abflusses  mit  seroser  Ausschwitzimg  beantworten. 

Als  Ursachen  der  Blutstockung  in  der  Lunge  werden  angef iihrt :  Storung 
des  Abflusses  des  Blutes  aus  den  Pulmonalvenen  und  ffeschwachte  Herz- 
action. 

1.  Storung  des  Abflusses  aus  den  Lungenvenen.  Als 
ein  typisches  Paradigma  von  behindertem  Abflusse  aus  den  Lungenvenen 
konnen  wir  beispielsweise  eine  Mitralstenose  betrachten.  Wie  allgemein 
bekannt,  kann  eine  betrachtliche  Verengerung  des  Mitralorificium  eine  Zeit 
lang  existiren  ohne  nennenswerthe  Storungen  von  Seiten  des  Gefasssystems. 
Dieser  Zustand  wird  das  Stadium  der  Compensation  genannt.  Wahrend 
desselben  stromt  durch  jeden  Querschnitt  der  gesammten  Gefassbahn 
dieselbe  Menge  Blut  in  der  Zeiteinheit  wie  unter  normalen  Verhaltnissen. 
Es  fliesst  deshalb  in  der  Zeiteinheit  von  den  Lungenvenen  durch  das  veren- 
gerte  Orificium  dieselbe  Menge  Blut  in  das  linke  Herz  wie  vorher  durch  das 
normal  weite  Ostium.  Wegen  der  vermehrten  Widerstande  muss  der  rechte 
Yentrikel  mit  grosserer  Kraft  arbeiten.  In  Folge  des  erschwerten  Abflusses 
und  der  vermehrten  Geschwindigkeit,  welche  das  rechte  Herz  der  ausge- 
triebenen  Blutmasse  ertheilt,  muss  der  Seitendruck  in  alien  Theilen  des 
Pulmonalgefasssystems  steigen.  Dass  unter  diesen  Umstanden  Lungen- 
odem  niemals  eintritt,  fiihrt  v.  I)  u  s  c  h  zu  der  Bemerkung  " :  ,,  Dass  das 
Lungenodem  nicht  oder  doch  nicht  vorzugsweise  durch  die  Drucksteigerung 
in  den  Lungenvenen  hervorgebracht  wird,  geht  daraus  hervor,  dass  in  den 
Fallen  hochster  Drucksteigerung  bei  geniigender  Compensation  em  relativ 
giinstiger  Zustand  fiir  den  Kranken  hergestellt  wird."  1st  v.  D  u  s  c  h 
berechtigt  anzunehmen,  dass  der  Druck  in  den  Lungenvenen  am  grossten 
in  dem  Stadium  der  Compensation  ist  ?  Die  Beantwortung  dieser  Frage  ist 
mit  grossen  Schwierigkeiten  verbunden.  v.  D  u  s  c  h  geht  von  der  Voraus- 
setzung  aus,  dass  die  Menge  Blut,  welche  ein  Ventrikel  in  der  Zeiteinheit 
empfangt,  allein  von  dem  Drucke  in  den  unmittelbar  vor  demselben  geleg- 
enen  Venea  abhangt,  und,  da  diese  Biutmenge  am  grossten  wahrend  der 
Compensation  ist,  so  schliesst  er,  dass  der  Venendruck  dann  am  hochsten 
sein  muss.  Die  Geschwindigkeit  aber,  mit  welclier  das  Blut  aus  den  Venen 
in  den  entsprechenden  Vorhof  einfliesst,  hangt  nicht  allein  von  dem  Drucke 
ab,  sondern  von  einer   Kraft,   welche   der  Summe   der  Widerstandshohe 

^  Lehrbuch  der  Herzkrankheiten.  S.  96.  Leipzig,  1868. 
4 


10       ZUR  PATHOLOGIE  DES  LUNGENODEMS 

(Seitendruck)  imd  der  Geschwindigkeitshohe  in  den  betreffenden  Yenen 
gleicht.    In  den  Korperarterien  ist  der  Werth  der  Geschwindigkeitshohe  im 
Vergleich  niit  der  Widerstandshohe  so  klein,  dass  er  bei  Druckmessungen 
vernachlassigt  wird,  aber  in  den  Venen,  wo  die  Widerstande  so  gering  sind, 
ist  derselbe  fiir  die  Fortbewegung  des  Blutes  nicht  ausser  Acht  zu  lassen. 
Im  Stadium  der  gestorten  Compensation  ist  die  bewegende  Kraft  des  rechten 
Ventrikels  vermindert ;  dem  entsprechend  ist  die  Spannung  in  der  Lungen- 
arterie  geringer  geworden,  aber  die  Gesanimtmenge  Blut,  welche  die  Lungen- 
enthalten,  kann  unverandert  bleiben  oder  sogar  vermehrt  werden.     Ent- 
sprechend der  verminderten  Spannung  in  den  Arterien  der  Lunge  vertheilt 
sich  das  Blut  anders ;  die  Lungenvenen  enthalten  mehr,  die  Arterien  weniger 
als  vorher.    Jetzt  gilt  es  die  schwierige  Frage  zu  erortern,  ob  diese  Vermeh- 
rung  des  Inhalts  der  Lungenvenen  eine  Drucksteigerung  in  denselben  zu 
Stande   bringt.      Setzen   wir   die   Geschwindigkeitshohe   in   den   Lungen- 
venen =G,  die  Widerstandshohe  =  W,  so  haben  wir  die  bewegende  Kraft  in 
denselben  K  =  W  +  G.     Sollte   die   Summe   W  +  G   den  Werth  erreichen, 
welchen  sie  wahrend  des  Compensationsstadiums  hat,  so  wiirde  bei  gleich- 
bleibenden   Widerstiinden   der  linke   Ventrikel   die  normale   Menge   Blut 
erhalten,  und,  vorausgesetzt  dass  seine  Kraft  unbeeintrachtigt  ist,  fortbe- 
wegen.    Deshalb  kann  der  Seitendruck  W  im  hochsten  Falle  um  eine  Grosse 
steigen,  welche  G  wahrend  der  Compensationsperiode  gleichkommt.     Der 
Werth  von  G  ist  uns  unbekannt.     Volkmann"*  berechnet  den  Werth 
der  Geschwindigkeitshohe  im   Anfange  der  Aorta   zu   8,2   Mm.   auf   die 
Hohe  einer   Blutsaule  bezogen.      Selbst  wenn   wir   annelmien,   dass   der 
Gesammtquerschnitt  der  Lungenvenen  nur  die  Halfte  dessen  der  Aorta  ist, 
so  wird  doch  die  Grosse  von  G  weniger  als  1|  Mm.  Quecksilber  betragen. 
Setzen  wir  ferner  voraus,  dass  die  Geschwindigkeitshohe  wahrend  des  Com- 
pensationsstadiums um  das  Mehrfache  gesteigert  sei,  so  wird  doch  immer 
der  Werth  von  G  so  klein  bleiben,  dass  die  Maximalgrenze  einer  vermuth- 
lichen  Druckerhbhung  bei  gestorter  Compensation  zu  niedrig  ausfallen  muss, 
um — im  Ilinblick  auf  die  unten  zu  berichtenden  Versuche  iiber  Pulmonal- 
druck  beim  Zustandekommen  von  Lungenodem — die  Entstehung  desselben 
bei  ungeniigender  Compensation  den  mechanischen  Hindernissen  und  der 
wegen  verminderter  Kraft  des  rechten  Ventrikels  geanderten  Vertheilung 
des  Blutes  allein  zuschreiben  zu  diirfen. 

Jeden  falls  steht  so  viol  fost,  dass  ein  betrjichtliches  Hinderniss  fiir  den 
Abfluss  des  Blutes  aus  den  Lungenvenen  existiren  kann,  ohne  dass  dadurch, 
80  lange  dieses  Hinderniss  durch  vermehrte  Arbeit  des  rechten  Ventrikels 
ausgeglichen  wird,  die  Entstehung  von  Lungenodem  herbeigefiihrt  wird. 

»  Die  H&modynamik.    S.  214.    Leipzig,  1850. 


ZUE  PATHOLOGIE  DES  LUNGENODEMS        11 

Wir  kommen  zu  der  letzten  der  oben  angefiihrten  Ursachen  des  Lungen- 
odems. 

2.  Gescliwachte  Herzaction.'^  Dieses  Moment  scheint  der 
Schwerpunkt  der  Sache  zu  sein.  Die  anderen  angeblichen  Ursachen  haben 
sich  nicht  als  causae  efficientes  erwiesen  und  konnten  im  besten  Falle  nur 
von  beschrankter  Bedeutung  sein  im  Vergleiche  mit  diesem  anscheinend 
allgemein  wirksamen  Factor.  Selbst  in  den  Fallen,  wo  andere  Verander- 
ungen  im  Spiele  sind,  hat  man  sich  doch  auf  Herzschwache  als  einen  mit- 
wirkenden  Factor  berufen,  well  in  der  That  in  der  Mehrzahl  der  Falle  von 
allgemeinem  Lungenodem  die  Thatigkeit  des  Herzens  herabgesetzt  ist. 
Wenn  wir  aber  annehmen,  dass  eine  allgemeine  Herzschwache  wirklich 
Lungenodem  herbeizufiihren  vermag,  so  ist  das  entstehende  Oedem  nicht 
die  Folge  einer  Drucksteigerung  in  den  Capillaren  und  Venen,  mit  anderen 
Worten  kein  Stauungsodem.  Es  ist  unmoglich,  dass  durch  Herzschwache 
der  Druck  in  den  Lungenvenen  die  Hohe  erreichen  soil,  welche  bei  unver- 
minderter  Herzkraft  in  den  Lungenarterien  herrscht.  Da  aber  nach  Unter- 
bindung  der  Venen  der  einen  Lunge,  diese  Venen  wie  blinde  Anhangsel  der 
entsprechenden  Arterie  zu  betrachten  sind,  so  muss  der  Druck  in  diesen 
derselbe  sein,  wie  in  der  Arterie  (oder  annahernd  derselbe,  indem  keine 
wesentliche  Erleichterung  seitens  der  Bronchialvenen  stattfindet,  wie,  von 
anatomischen  Griinden  abgesehen,  das  Auftreten  von  vollstandiger,  hamor- 
rhagischer  Infarcirung  der  betreffenden  Lunge  beweist)  und  doch  entsteht 
unter  diesen  Umstanden  niemals  Oedem."  Da  in  dem  analogen  Falle  im 
Korperkreislauf,  wo  sammtliche  von  einer  Extremitat  abfiihrenden  Venen 
zugebunden  werden,  Oedem  entsteht,  so  miissen  wir  den  Lungencapillaren 
im  Verhaltnisse  zum  Drucke  im  Pulnionalkreislauf  eine  grossere  relative 
Impermeabilitat  zurechnen,  als  den  Capillaren  anderer  Organe. 

Ist  aber  die  Folge  der  Herzschwache  Lungenodem?  Die  nothwendige 
Folge  ist  es  unbedingt  nicht.  Eine  Syncope  kann  noch  so  lange  dauern 
imd  fiihrt  niemals  zum  Hydrops  pulmonum.  Durch  Vagusreizung  konnen 
wir  die  bewegende  Kraft  des  Herzens  vernichten,  so  dass  die  Spannung  in 
den  Gefassen  der  des  ruhenden  Blutes  gleich  wird  und  es  entstehen  nicht 
die  geringsten  Zeichen  eines  Lungenodems.  In  den  allerseltensten  Fallen 
iiberhaupt  ist  der  Tod  die  Folge  eines  plotzlichen  Erloschens  der  Herzkraft ; 
diese  sinkt  vielmehr  allmahlich  von  ihrer  normalen  Grosse  bis  auf  Null, 
und  doch  sterben  nicht  alle  Menschen  an  Lungenodem.     Aber,  erwidert 

"  Was  ich  hier  iiber  Herzschwache  zu  sagen  habe,  bezieht  sich  ausschliesslich 
auf  die  gewohnliche  Auffassung  dieses  Zustandes,  scil.  eine  gleichzeitige  und 
gleichmassige  Schwachung  beider  Herzhalften.  Eine  Schwachung,  bei  welcher 
die  Kraft  des  einen  Ventrikels  verhaltnissmassig  weniger  herabgesetzt  wird, 
als  die  des  anderen,  lasse  ich  vorlaufig  ausser  Betracht. 

='  C  0  h  n  h  e  i  m  ,  Op.  cit.  S.  419. 


12       ZUR  PATHOLOGIE  DES  LUNGENODEMS 

man,  wenn  Lungenodem  eintreten  soil,  muss  die  Herzschwache  lange  dauern ! 
Als  eine  derartige  in  der  That  nicht  seltene  Folge  der  Herzschwache,  welche 
Tage  und  Wochen  lang,  besonders  bei  cachechtischen  und  fieberhaften  Krank- 
heiten,  gedauert  hat,  wird  das  sogenannte  hypostatische  Oedem  vielseitig 
aufgefasst.  Ein  Hauptmerkmal  aber  des  allgemeinen  Lungenodems  ist  eben 
sein  acutes  Auftreten,  welches  fiir  einc  plotzlich  eintretende  Ursache  spricht, 
und  in  vielen  Fallen  ist  dem  Lungenodem  keine  langdauernde  Herz- 
schwache vorhergegangen.  Die  Beobachtung  am  Menschen  berechtigt  uns 
deshalb  zu  dem  Schlusse,  dass  eine  Erniedrigung  der  Herzkraft  an  und  fiir 
sich  kein  Oedem  erzeugt,  das  Experiment  wird  uns  lehren,  dass  eine  Schwiich- 
ung  des  rechten  Ventrikels  in  gewissem  Sinne  sogar  ein  ungiinstiges  Moment 
fiir  das  Zustandekommen  von  Lungenodem  ist, 

Ich  hal>e  im  Vorhergehenden  die  gangbaren  Anschauungen  liber  die 
Ursachen  von  Lungenodem  einer  Kritik  unterzogen,  und  wir  kommen  nun- 
mehr  zu  dem  Schlusse,  dass  keine  uns  eine  geniigende  Erklarung  darbietet. 
Obwohl  die  meisten  der  oben  enviihnten  Bedinguugen  aui  falschen  theo- 
retischen  Voraussetzungen  begriindet  worden  sind,  bin  ich  denselben  doch 
so  wenig  wie  moglich  von  theoretischen  Gesichtspunkten  und  so  viel  wie 
moglich  von  Seiten  der  Beobachtung  und  des  Versuches  entgegengetreten. 
Sollen  wir  nun  aber  von  alien  mechanischen  Momenten  absehen  und  die 
Ursachen  des  allgemeinen  Lungenodems  in  anderen  Bedingungen  suchen? 
Es  scheint  allerdings,  als  ob  nach  unseren  bisherigen  Betrachtuugen  dem 
Lungenodem  eine  ganz  aparte  Stellung  im  Vergleich  mit  den  Wassersuchten 
anderer  Korpertlieile  einzuraumen  sei.  Bei  dieser  Lage  der  Sache  konnen 
wir  nur  durch  das  Experiment  einer  Losung  des  complicirten  Problems 
etwas  naher  zu  treten  hoffen. 

Die  erste  zu  beantwortende  Frage  ist:  Giebt  es  iiljerhaupt  ein  Stauungs- 
odem  in  der  Lunge?  Denn  eigentlich.  haden  wir  bis  jetzt  keineu  Grund 
gefunden,  die  Existenz  desselben  beim  Menschen  anzunehmen. 

Eine  Stauung  in  der  Lunge  konnen  wir  zu  Stande  bringen  durch  Hinder- 
nisse  in  den  Lungenvenen,  in  dem  linken  Vorhofe,  in  dem  linken  Ventrikel 
und  in  der  Aorta. 

Die  Versuche  wurden  an  Kaninchen  und  an  Hunden  gemacht.  Hunde 
bieten  den  Vortheil,  dass  an  ihnen  der  Druck  in  der  Pulmonalarterie  leicht 
zu  messen  ist.  Bei  Kaninchen  entsteht  andererseits  Lungenodem  leichter 
als  bei  Hunden.  Bei  beiden  Tliiercn  giebt  die  Aorta  zuerst  den  Truncus 
anonymus  ab,  von  welchem  die  linke  Carotis,  die  rechte  Subclavia  und  die 
rechte  Carotis  ihren  Ursprung  zu  nehmen  pflegen.  Der  zweite  Hauptast 
der  Aorta  ist  die  linko  Subclavia. 

Wenn  man  einem  Kaninchen  den  Aortenbogen  zwischen  dem  Truncus 
anonymus  und  der  linken  Subclavia  unterbindet,  so  wird  das  Thier  an  den 


ZUR  PATHOLOGIE  DES  LUNGENODEMS        13 

hinteren  und  der  linken  vorderen  Extremitat  gelahmt  und  leidet  wegen 
Lahmung  des  Zwerchfells  und  der  Musculi  intercostales  an  starker  Dyspnoe. 
Nach  ^ — 1  Stunde  stirbt  es,  ohne  dass  besondere  Veranderungen  an  den 
Lungen  zu  bemerken  sind.  Mit  Hiilfe  der  kiinstlichen  Athmung,  welche 
in  fast  alien  diesen  Versuchen  benutzt  wurde,  lebt  das  Thier  langer,  jedoch 
gleichfalls  ohne  dass  die  Lungen  nach  dem  Tode  etwas  Bemerkenswerthes 
darbieten.  Wenn  gleiehzeitig  die  eine  Carotis  communis  durch  eine  end- 
fetiindige  Maiiometercaniile  verlegt  wird,  so  steigt  der  Druck  in  derselben  um 
50  bis  100  pCt.  liber  seine  normale  Hohe.  In  diesem  Falle,  wo  bios  die 
andere  Carotis  und  die  rechte  Subclavia  oifen  sind,  habe  ich  gewohnlich  kein 
Lungenodem  nach  dem  Tode  gefunden;  gelegentlich  jedoch,  besonders  bei 
jungen  Kaninchen,  erfolgt  ein  massiges  Oedem.  Erst  wenn  der 
Aortenbogen  zwischen  Truncus  anonym  us  und  linke 
Subclavia  und  zwei  Aeste  des  Truncus  anonymus 
geschlossen  werden,  d.  h.  wenn  die  einzige  Abfluss- 
rohre  a  us  der  Aorta  (die  Kranzarterien  ausgenommen)  die  eine 
Carotis  oder  die  rechte  Subclavia  bildet,  entsteht 
ganz  regelmassig  Lungenodem.  Das  Thier  wird  gleich  nach 
der  Unterbindung  unruhig,  in  1  —  3  Minuten  bekommt  es  Krampfe  und 
stirbt  unter  den  bekannten  Erstickungserscheinungen,  Wenn  man,  wie  C. 
Friedlander"  schon  gethan  hat,  die  Aorta  zwischen  dem  Herzen  und 
dein  Truncus  anonymus  zuklemmt  oder  unterbindet,  so  stirbt  das  Thier 
nach  einigen  Secunden  mit  heftigen  Krampfen,  und  die  Untersuchung  der 
Lungen  gleich  nach  dem  Tode  zeigt  starkes  Oedem.  Die  Lungen  werden 
grosser  und  blutreicher  als  normal  gefunden,  und  aus  der  Trachea  und  den 
Bronchien  fliesst  eine  schaumige,  wassrige  Fliissigkeit  von  gelblichem  oder 
gelblich-rothlichem  Farbenton  aus.  Wenn  man  die  Trachea  zuerst  offnet, 
ohne  die  Lungen  zu  beriihren,  findet  man  nicht  selten  gar  keine  serose 
Fliissigkeit  in  derselben;  doch  geniigt,  wenn  Oedem  vorhanden  ist,  ein 
leichter  Druck  auf  die  Lungen,  um  das  serose  Tl-anssudat  herauszupressen. 
Die  Unterbindung  der  oben  genannten  Arterien  bietet  keine  Schwierig- 
keiten.  Der  Hautschnitt,  welcher  vorher  gemacht  worden  ist,  um  die 
Trachealcaniile  einzusetzen,  wird  in  der  Mittellinie  bis  zu  3 — 4  Cm.  unter- 
halb  des  oberen  Sternalrandes  verlangert.  Obwohl  es  moglich  ist,  die  Aorta 
und  die  Aeste  des  Truncus  anonymus  mit  gekriimmten  Haken  von  oberlialb 
des  Sternums  her  zu  erreichen,  wird  doch  die  Operation  um  Vieles  erlichtert, 
wenn  man  die  Crista  an  dem  oberen  Theile  des  Sternums  abschneidet  und 
das  Sternum  in  der  Ausdehnung  von  1 — 2  Cm.  mit  starker  Scheere  spaltet. 
Dies  geht  ohne  Blutung  vor  sich,  wenn  der  Schnitt  in  der  Mittellinie  gef  iihrt 

''  Op.  cit. 


14       ZUK  PATHOLOaiE  DES  LUNGENODEMS 

wird.  Will  man  die  Aorta  dicht  am  Herzen  unterbinden,  so  muss  man  das 
Sternum  weiter  spalten  und  den  oberen  Theil  des  Herzbeutels  eroffnen. 
Mit  einiger  Sorgfalt  kann  man  sehr  gut  das  Brustbein  bis  zum  Ansatz  des 
Zwercbfells  in  der  Mittellinie  spalten,  ohne  dass  eine  von  beiden  Pleura- 
holilen  geoffnet  wird.  Nachdera  die  im  vorderen  Mediastinum  gelegene 
Driisen-  und  Fettmasse,  welche  den  Aortenbogen  und  seine  Aeste  bedeckt, 
mittelst  Pineetten  zerrissen  worden  ist,  liegen  diese  frei  zu  Tage. 

Versuch,  welche  den  Zweck  batten  zu  untersuchen,  um  wie  viel  es  nothig 
sei  die  aufsteigende  Aorta  zu  verengern,  um  Oedem  zu  erzeugen,  ergaben, 
dass  das  Lumen  der  Aorta,  fast  zu  Verschluss  verengert  werden  muss,  ehe 
Lungenodem  eintritt. 

Bei  diesen  Versuchen  machte  ich  die  interessante  Beobachtimg,  dass  bei 
Kaninchen  Yerengenmg  des  aufsteigenden  Aortenbogens  bis  zu  einem 
gewissen  Grade  eine  Drucksteigerung  jenseits  (peripher)  der  verengten  Stelle 
bewirkt.  Um  die  Arterie,  ohne  Zerrung  der  anliegenden  Gebilde,  zu  veren- 
gen,  wurde  ein  G  r  a  e  f  e  '  scbes  Ligaturstabchen  benutzt,  welches  Ver- 
kleinerung  des  Gefasslumens  in  jedem  beliebigen  Grade  bis  zur  voll- 
standigen  Versehliessung  erlaubt.  Als  ein  Beispiel  fiir  das  interessante 
Verhalten  des  Carotisdruckes  nach  Verengerung  der  aufsteigenden  Aorta, 
f  iilire  ich  das  Folgende  aus  einem  Versuchsprotokoll  an. 

Yersuch  1.  Grosses  Kaninchen.  Tracheotomie.  Kiinstliche  Ath- 
mung.  Quecksilbermanometer  in  Verbindung  mit  rechter  Carotis.  Druck 
schwankt  zwischen  100  und  115  !Mm.  Brustbein  in  der  Mittellinie  gespal- 
ten,  Aortenbogen  freigelegt,  Herzbeutel  geoffnet.  Starker  Faden  um  die 
Aorta  zwischen  Herz  und  Truncus  anonymus  gelegt  und  an  dem 
G  r  a  e  f  e '  schen  Ligaturstabchen  befestigt.  Durch  Zuschraubung  wird  die 
Aorta  allmahlich  verengert,  wodurch  der  Druck  in  der  Carotis  von  100  bis 
zu  140  Mm.  steigt.  Bei  weiterer  Verengerung  bleibt  der  Druck  einige  Zeit 
auf  dieser  Hobe  xmd  dann,  nachdem  die  Verkleinerung  des  Gefassquer- 
schnitts  einen  gewissen  Grad  iiberschritten  hat,  fangt  er  an  allmahlich  zu 
sinken.  Eine  Wioderholung  des  Versuches  giebt  dasselbe  Resultat.  Ge- 
wobnlich  aber  nach  Wiedereroffnmig  des  Gefasslumens  steigt  der  Druck 
etwas  iiber  seinen  friiheren  Werth  (auf  130 — 140)  und  sinkt  dann  wieder  bis 
zu  einem  Puiikte  zwischen  100 — 115.  Als  der  Faden  noch  fester  zuge- 
schniirt  wird,  so  dass  das  Gefiisslumen  fast  ganz  verschlossen  ist,  bekommt 
das  Thier  Kriimpfe;  der  Knot«n  um  die  Aorta  wird  gleich  losgemacht,  so 
dass  die  Arterie  ihre  normale  Weite  wieder  erhalt.  Wahrend  der  Er- 
stickungskrampfe  steigt  der  Druck  bis  zu  180  und  zeigt  die  bekannten 
rhythniiscben  Scliwankungen.  Nach  den  Krampfen  ist  das  Thier  beweg- 
\uigslos  und  unerreg])ar,  athmet  niclit  selbsttindig,  Druck  120.  Jetzt  bei 
jedor  Verengerung  dor  Aorta  sinkt  der  Druck  pari  passu  in  der  Carotis, 
und  obwohl  das  Thier  sich  etwas  crholt,  so  dass  es  sell)standig  athmet  und 
die  ITornbaut  etwas  erregljar  wird,  bringt  doch  eine  Aorten verengerung 
nicht  mehr  eine  Drucksteigerung  in  der  Carotis  zu  Stande.    Das  Thier  wird 


ZUR  PATHOLOGIE  DES  LUNGENODEMS        15 

getodtet  durch  Einspritzung  von  Curare  in  die  Vena  jugulaxis  ext.,  um 
eine  plotzliche  Herzlahmung  wahrend  massiger  Verengerung  der  Aorta  zu 
erzeugen.     Die  Obduction  ergiebt  kein  Lungenodem. 

Diese  Drucksteigerung  nach  Verengerung  der  Strombahn  aus  dem  linken 
Ventrikel  ist  wahrscheinlich  derselben  Natur  wie  diejenige,  welche  S. 
Mayer"  nach  Unterbindung  der  Hirnarterien  beobachtet  hat,  und  einer 
Reizung  der  vasomotorischen  Centren  durch  Hirnanamie  zuzuschreiben. 
Man  konnte  auch  an  eine  Eeizung  des  linken  Ventrikels  denken,  durch 
welche  derselbe  zu  grosserer  Arbeit  erregt  wird,  als  um  die  vermehrten 
Widerstande  zu  iiberwinden  nothig  sei.  Dafiir  spricht  vielleicht  der 
Umstand,  dass  nach  Herstellung  der  normalen  Gefassweite  der  Druck  iiber 
seine  normale  Hohe  steigt  (in  einem  Falle  von  100  bis  zu  160),  Es  ist 
von  Interesse  zu  bemerken,  dass  in  dem  obigen  Versuche,  nachdem  die 
allgemeine  Erregbarkeit  vernichtet  worden,  die  Drucksteigerung  ausblieb 
welches  Verhalten  vielleicht  einer  gleichzeitigen  Unerregbarkeit  der  vasomo- 
torischen Centren  zugeschrieben  werden  kann.  Bei  verschiedenen  Kaninchen 
f allt  die  Druckerhohung  sehr  ungleichmassig  aus ;  bei  Hunden  habe  ich  sie 
iiberhaupt  nicht  beobachtet. 

Was  lehren  diese  Versuche  iiber  die  Entstehung  von  Lungenodem  ?  SoUen 
wir  annehmen,  dass  ein  Widerstand  fiir  den  Abfluss  des  Blutes  aus  der 
Aorta,  welcher  den  Carotisdruck  um  das  Zweifache  erhoht,  keine  Stauung 
in  der  Lunge  verursacht,  oder  dass  die  Stauung  nicht  ausreicht,  um  Oedem 
zu  Stande  zu  bringen  ?  Diese  Fragen  sind  zu  beantworten  nur  durch  Mes- 
sung  des  Pulmonaldruckes  wahrend  Verschliessung  der  Aorta  oder  ihrer 
Aeste.    Zu  diesem  Zwecke  wurden  Versuche  an  Hunden  angestellt. 

L  i  c  h  t  h  e  i  m  hat  gefunden,  dass  nach  Unterbindung  der  Brustaorta 
dicht  iiber  dem  Zwerchfell  bei  undurchschnittenem  Halsmarke  der  Druck 
in  der  Lungenarterie  unverandert  bleibt,  wahrend  der  Carotisdruck  bekannt- 
lich  bedeutend  steigt.  Meine  Versuche  haben  seine  Resultate  nicht  nur 
bestatigt,  sondern  sogar  ergeben,  dass  der  Druck  in  beiden  Arteriensystemen 
in  noch  hoherem  Grade  von  einander  unabhangig  ist,  als  aus  jenen  Ver- 
suchen  hervorgeht. 

Das  Verfahren  bei  Messung  des  Lungenarteriendruckes  war  im  "\Yesent- 
lichen  dasselbe,  welches  Lichtheim  benutzte,  auf  dessen  Beschreibung 
ich  verweise.""  Ich  legte  aber  das  Fenster  in  der  linken  Thoraxhalfte  hoher 
als  er,  nehmlich  zwischen  erster  und  vierter  oder  zweiter  und  fiinfter  Rippe, 
well  von  einem  solchen  Fenster  sowohl  die  Aorta  in  ihrer  ganzen  Lange 
bis  zum  Zwerchfell  wie  deren  Aeste  ohne  grosse  Schwierigkeit  zuganglich 
sind.     Man  kann  von  derselben  Thoraxoffnung,  welche  fiir  Druckmessung 

=■■  Wiener  Sitzungsberichte.  LXXIII.  Abth.  III.   S.  85. 
^^  Op.  cit.  S.  26. 


16        ZUR  PATHOLOGIE  DES  LUNGENODEMS 

in  dem  zum  unteren  Lappen  gehenden  Aste  der  linken  Lungenarterie  dient, 
den  Tnmcus  anonymus  oder  seine  drei  Aeste,  die  linke  Subclavia  und  den 
Aortenbogen  an  irgend  einer  beliebigen  Stelle  zuklemmen  oder  unter- 
binden.  Wenn  man  diese  Gefasse  ohne  Oellfnung  einer  Pleurahohle 
erreichen  will,  dann  ist  dasselbe  Verfahren  wie  bei  Kanincben  anwendbar, 
i.  e.  Spaltung  des  Brustbeins  in  der  Mittellinie.  AVegen  der  grosseren  Tiefe 
des  Yorderen  Mediastinums  bei  Hunden  ist  es  empfehlenswerth,  nach  Eroff- 
nung  des  Thorax  in  der  j\Iittellinie  die  Arteriae  mammariae  gleich  zu  unter- 
binden,  weil  sie  bei  Blosslegung  der  grossen  Arterienstiimme  leicht  verletzt 
werden  koimen.  Mit  Ausnahme  einiger  Controlversuche  waren  sammt- 
liche  Versnche  an  curarisirten  Hmiden  angestellt,  die  durch  kiinstliche 
Athmung  am  Leben  erhalten  wurden.  Bei  alien  Versuchen  wurden  die 
Arterien  nach  dem  Tode  von  dem  linken  V'entrikel  oder  Anfangstheile 
der  Aorta  aus  mit  einer  Aufsehwemmiing  von  chromsaurem  Blei  ausgespritzt. 
Dieses  Verfahren  ist  unbedingt  nothig,  erstens  um  zu  beweisen,  dass  die 
Arterien  an  den  Unterbindungsstellen  festverschlossen  sind  und  zweitens  um 
festzustellen.  ob  andere  Wege,  als  man  glaubt,  offen  geblieben  sind.  Die 
Aorta  besonders  muss  sehr  fest  zugebunden  werden.  In  seltenen  Fallen 
nimmt  die  reehte  Subclavia  von  dem  Aortenbogen  selbst,  hinter  der  linken 
Subclavia,  ihren  Ursprung. 

Obwohl  Lichtheim  nachgewiesen  hatte,  dass  Oeffnung  einer  Pleura- 
hohle keinen  Einfluss  auf  den  Pulraonal-  oder  Carotisdruck  ausiibt,  machte 
ich  doch  zuerst  die  Versuche  ohne  Pneumothorax,  aber  die  Ergebnisse 
waren  dieselben  wie  bei  offenem  Thorax. 

Um  die  Grenze  zu  finden,  bei  welcher  die  Hindernisse  fiir  den  Ausfluss 
des  Blutes-au?  dem  linken  Ventrikel  hinreichend  gross  sind,  um  Lungen- 
odem  zu  Folge  zu  habcn,  wurden  zuerst  die  Aorta  peripher  von  der  linken 
Subclavia,  dann  gleichzeitig  die  linke  Subclavia  selbst  und  endlich  die 
Aeste  des  Truncus  anonvTnus  unterbunden.  In  einer  nicht  unbedeutenden 
Anzahl  von  Versuchen  ist  es  mir  nicht  gelungen  Lungenodem  bei  Hunden 
zu  erzielen,  ehe  jeder  Ausfluss  aus  dem  Aortenbogen  abgeschlossen  worden 
war.  Entweder  muss  der  Aortenbogen  zwischen  dem  Herzen  und  der 
Ursprungsstelle  des  Truncus  anonynms,  oder  gleichzeitig  alle  vorher  abge- 
gebenen  Aeste  verschlossen  werden. 

Versuch  2.  ]\Iittelgrosser,  curarisirter  Hund.  Arterien,  ohne, 
Verletzung  der  Pleura,  in  der  folgenden  Reihe  verlegt.  Endstandige  Hg.- 
Manometcrcaniile  in  linker  Carotis  communis,  Unterbindung  der  linken 
Subclavia  nalie  an  ihrem  I^rsprung.  der  Aorta  dicht  jenseits  der  letzteren, 
der  rechten  Carotis  communis  und  der  rechten  Subclavia  dicht  peripher 
von  der  Art.  vertebral  is.  Der  Carotisdruck  steigt  von  80  bis  zu  320  Mm. 
Die  Pulse  sind  von  Zeit  zu  Zeit  durch  T  r  a  u  b  e  '  sche  Wellen  unterbrochen. 
Erst  nach  einer  Stunde  ist  der  Carotisdruck  bis  ungefahr  Null  gesunken.    Die 


ZUE  PATHOLOGIE  DES  LUNGENODEMS        17 

Section  ergiebt  kein  Lungenodem.  Einspritzung  mit  chromsaurem  Blei 
zeigt,  dass  die  Art.  vertebralis  dextra  der  einzige  offene  Weg  fiir  das  Blut 
aus  der  Aorta  gewesen  ist. 

Versuch  3.  Mittelgrosser,  curarisirter  Hund  mit  Hg.-Manometer 
in  Verbindung  mit  linker  Carotis  und  mit  dem  unteren  Aste  der  linken 
Lungenarterie.  Carotisdruck  80 — 90.  Lungenarteriendruck  18  Mm. 
Unterbindung  der  linken  Subclavia  nalie  an  ihrer  Ursprungsstelle.  Druck 
in  beiden  Arterien  unverandert.  Unterbindimg  der  Aorta  dicht  jenseits 
der  linken  Subclavia.  Carotisdruck  steigt  von  80  bis  zu  160  Mm.  Lungen- 
arteriendruck bleibt  unverandert.  (Vago-sympathici  durchschnitten  um 
die  grossen  Druckscliwankungen  zu  beseitigen^)  Unterbindung  des  Truncus 
anonymus  dicht  an  seiner  Ursprungsstelle.  Der  Druck  in  der  Lungen- 
arterie  steigt  von  18  Mm.  bis  zu  60  Mm.  Hg.  Xach  5  Minuten  sinkt  er 
allmahlich  zu  16  Mm.  Section  ergiebt  starke  Stauung  und  Oedem  beider 
Lungen. 

In  diesem  Falle  erreichte  der  Pulmonalisdruck  nach  Unterbindung  der 
Aorta  und  seiner  Aeste  eine  Hohe,  welche  imgefahr  das  3-|  fache  seines 
urspriinglichen  Werthes  betragt.  Nach  Unterbindung  der  Aorta  allein 
dicht  peripher  von  der  Art.  subclavia  sinistra  entsteht  entweder  keine 
Veranderung  in  dem  Drucke  der  Lungenarterie  oder  er  steigt  im  hochsten 
Falle  4 — 5  Mm.  Quecksilber.  Diese  kleinen  Druckveranderungen  werden 
natlirlich  am  besten  an  einem  Sodamanometer  studirt.  In  einem  Versuche, 
in  welchem  die  einzig  offen  gebliebene  Arterie  rechte  Subclavia  war,  stieg 
der  Pulmonalisdruck  von  180  (seiner  urspriinglichen  Hohe)  bis  zu  230 
Mm.  Soda  (bios  4  Mm,  Hg.).  In  einem  anderen  Versuche,  in  welchem 
mit  Ausnahme  der  linken  Subclavia  jeder  Abfluss  aus  dem  Aortenbogen 
verschlossen  worden  war,  stieg  der  Pulmonaldruck  von  170  Mm.  Soda  bis 
zu  230  Mm.  (35^  pCt.),  wahrend  der  mit  einem  endstandigen  Manometer 
gemessene  Druck  in  der  Carotis  von  60  bis  zu  230  Mm.  Quecksilber 
(300  pCt.)  gestiegen  war. 

Diese  erstaunliche  Immunitat  des  Pulmonalkreislaufs  gegen  Druck- 
veranderungen im  Korperkreislauf  giebt  uns  die  Antwort  auf  die  oben  aufge- 
worfene  Frage.  Das  Ausbleiben  von  Lungenodem  bei  solchen  Hindemissen, 
welche  den  Carotidendruck  zwei-  bis  vierfach  erhohen  konnen,  ist  kein 
Beweis,  dass  eine  Stauung  in  der  Lunge  kein  Oedem  zu  Folge  hat,  da  solche 
colossale  Widerstande  existiren  konnen,  ohne  dass  eine  irgend  betrachtliche 
Steigerung  des  Druckes  im  kleinen  Kreislauf  statthat;  es  beweist  im  besten 
Falle  bios,  was  wir  schon  von  der  Beobachtung  am  Menschen  wussten,  dass 
ein  gewisser  Grad  von  Lungenstauung  vorhanden  sein  kann,  ohne  Oedem 
herbeizufiihren.  Lungenodem  entsteht  bei  Kaninchen,  wenn  die  eine  Carotis 
Oder  die  eine  Subclavia  die  einzige  Ausflussrohre  bildet,  imd  bei  Hunden, 
wenn  der  Abfluss  noch  mehr  erschwert  wird,  und  erst  bei  solcher  Einen- 
gmig  der  Gefassbahnen  erleidet  der  Pulmonaldruck  eine  bedeutende 
Steigerung ! 


18  ZUR  PATHOLOGIE  DES  LUNGENODEMS 

DasErgebnissderVersuchebetreffsTJnterbindung 
der  grossen  A  r  t  e  r  i  ens  t  a  mme  ist  also,  dass  durch 
dieselbe  Lungenodem  und  zwar  ein  S  t  a  u  un  gso  d  em 
erzeugt  werden  kann,  dass  aber  eine  bedeutende 
Stauung  in  der  Lunge  in  Folge  van  W  il  d  e  r  s  ta  n  d  en 
i  m  grossen  Kreislaufe  erste  dann  entsteht,  wenn 
diese  eine  Hohe  erreicht  haben,  von  welcher  beim 
Menschen  kaum  die  Rede  sein  kann. 

Diese  Stauung  ist,  wie  jede  Stauung,  dadurch  bedingt,  dass  mehr  Fliissig- 
keit  zufliesst  als  abfliessen  kann.  Die  Krafte,  welehe  das  Blut  noch  in's 
reehte  Herz  treiben,  nachdem  die  bewegende  Kraft  des  linken  Ventrikel.s 
zum  gTossten  Theile  oder  ganzlich  aufgehoben  worden  ist,  sind  die  hohere 
arterielle  Spannung,  der  Gefasstonus  und  moglicherweise  eine  saugende 
Wirkunjr  des  rechten  Ventrikels.  Dass  der  Gefasstonus  von  Einfluss  bei 
diesem  Vorgange  ist,  beweisen  die  Versuche  von  G  o  1 1  z  ,'°  und  die  Beo- 
baehtung  von  B  e  z  o  1  d  und  G  s  c  h  e  i  d  1  e  n  ,'"  welehe  fanden,  dass  nach 
Ab^^perrung  des  Bhitai)flusses  aus  dem  linken  Ventrikel  der  venose  und  der 
arterielle  Druek  sich  langsamer  ausgleichen,  wenn  der  Gefasstonus  durch 
Durchschneidung  des  Halsmarkes  herabgesetzt  wird.  Als  ich  bei  einem 
TTunde  die  Aorta  dieht  hinter  der  linken  Subclavia  zuklemmte,  sank  der 
Druck  gleichzeitig  in  der  Arteria  femoralis  (von  100  bis  zu  20  Pig.)  und 
in  der  Vena  femoralis  (von  30  bis  zu  15  Soda),  wahrend  er  sowohl  in  der 
Vena  jugularis  externa  (von  5  bis  zu  25  Soda),  wie  in  der  Carotis  communis 
(von  100  bis  zu  150)  stieg.  Dagegen  nach  Zuklemmung  der  Aorta  zwischen 
linkem  Ventrikel  und  Truncus  anonymus  stieg  der  Druck  in  der  Vena 
jugularis  und  der  Vena  femoralis  (in  der  ersteren  von  0 — 5  bis  zu  50  Soda, 
in  der  letzteren  nicht  genau  mcssbar  wegen  ungeniigender  Lange  der  Mano- 
meterrohre).  Ob  bei  Zuklemmung  hinter  der  linken  Subclavia  die  Vermeh- 
rung  des  Zuflusses  zum  Herzen  durch  die  obere  Hohlvene  die  Verminderung 
desselben  durch  die  untere  Hohlvene  deckt,  muss  ich  dahingestellt  lassen, 
dafiir  aber  spricht  die  Unveranderlichkeit  des  Pulmonaldruckes,  Bei  Ver- 
schluss  der  Aorta  ascendens  andererseits  ist  die  Drucksteigerung  in  den 
Korpervenen  am  wahrscheinlichsten  der  Stauung  im  kleinen  Kreislauf 
zuzuschreiben. 

Von  besonderem  Interesse  ware  es  zu  constatiren,  in  welcher  Weise  das 
Zustandekommen  von  Lungenodem  bei  Unterbindmig  der  Arterien  durch 
die  Ilerzkraft  beciiiflusst  sei.  In  Anblick  der  geliiufigen  Anschauungen  iiber 
die  Bedeutung  von  Herzschwiiche  als  eine  Ursache  von  Lungenodem,  konnte 

"Virchow's  Archiv  Bd.  28,  S.  428.     1864. 

*•  Untersuchungen  aus  dem  physiol.  Laboratorium  in  Wurzburg.     1867.    Hft.  2. 


ZUE  PATHOLOGIE  DES  LUNGENODEMS        19 

man  vielleicht  genei^  sein  zu  glauben,  dass  eine  Verminderang  der  Herz- 
kraft  die  Entstehung  von  Lungenodem  bei  diesen  Experimenten  begiingstigt 
hatte."  Andererseits  ware  aber  zu  erwagen,  ob  nicht  vielmehr  eine  grosse 
Schwache  des  rechten  Ventrikels  ein  Hinderniss  fiir  das  Zustandekommen 
derjenigen  Drucksteigenmg  in  der  Lunge  sein  muss,  welche  fiir  die  Entste- 
hung von  Oedem  nothig  ist.  Oefter  als  erwiinscht  war  die  Gelegenheit 
vorhanden,  die  Probe  auf  diese  Ueberlegung  zu  machen.  Bei  Hunden, 
denen  entweder  zu  viel  Curare  eingespritzt  war,  oder  bei  welchen  die  Opera- 
tion mit  offener  Pleurahohle  lange  gedauert  hatte,  wurde  oftmals  die 
Herzkraft  so  niedig  (oder,  wie  von  einigen  Beobachtungen  wahrscheinlicher 
.ist,  der  rechte  Ventrikel  so  unerregbar),  dass  TJnterbindung  des  Aorten- 
bogens  und  aller  seiner  Aeste  kein  Oedem  mehr  erzeugte.  Dem  entsprechend 
stieg  der  Druck  in  der  Pulmonalart^rie  weniger  als  in  den  Fallen,  wo  Oedem 
eintritt. 

Versuch  4.  Bei  einem  tief  curarisirten  kleinen  Hunde  war  2  Stun- 
den  nach  Anfang  der  Operation  der  Carotisdruek  bis  zu  30  Mm.  Hg. 
gesunkcn,  als  die  Arterien  in  der  f olgenden  Eeihe  unterbunden  wurden : 
Truncus  anonymus  zwischen  linker  Carotis  und  rechter  Subclavia,  linke 
Subclavia  vor  Abgabe  eines  Astes,  und  die  Aorta  dicht  hinter  der  linken 
Subclavia.  Da  eine  Manometercaniile  in  der  linken  Carotis  steckt,  so  ist 
der  grosse  Kreislauf  jetzt  vollkommen  unterbrochen.  Die  linke  Carotis 
zeigt  zuerst  hohen  Druck  mit  colossalen  Schwankungen.  Durch  die  Systole 
wird  der  Druck  bis  zu  340  Mm.  Hg.  getrieben,  wahrend  der  langdauernden 
Diastole  sinkt  er  auf  40  Mm.  Dabei  ist  ein  ausgesprochener  Pulsus  bige- 
minus  vorhanden.  Nach  diesen  grossen  Schwankimgen  tritt  eine  Periode 
eine  von  hohem  Drucke,  schnellem  Pulse  und  kleinen  Schwankungen 
(Mitteldruck  250 — 260  Mm.).  Diese  zwei  Arten  von  Perioden  alterniren 
in  je  10  Minuten.  ISTach  einer  halben  Stunde,  wahrend  welcher  die  kiinst- 
liche  Athmung  erhalten  worden  ist,  ist  der  Druck  bis  auf  50  Mm.  gesunken. 

Nach  Unterbindung  der  Arterien  bleibt  der  Pulmonaldruck  anderthalb 
Minuten  unveriindert,  dann  fangt  er  an  zu  steigen  und  im  Laufe  von  3 — 4 
Minuten  erreicht  er  eine  Hohe  von  35  Mm.  Hg.,  von  welcher  er  bald  wieder 
auf  18  Mm.  sinkt.    Es  entstand  kein  Oedem. 

Obwohl  ein  Druck  von  35  Mm.  Hg.  in  der  Pulmonalarterie  nach  den 
Messungen  von  Lichtheim  und  von  mir  immerhin  ein  hoher  genannt 
werden  muss,  ist  er  doch  nicht  zu  vergleichen  mit  dem  Drucke,  welcher  in 
den  Versuchen  zu  Stande  kam,  wo  das  Herz  bei  der  Gefassunterbindung 
kraftig  war  und  Lungenodem  entstand  (cfr.  Vers.  3).  Das  Ausbleiben  von 
Lungenodem  in  diesen  Fallen,  wo  die  sonstigen  Bedingungen  vorhanden 

'^Wie  es  kaum  nothig  zu  betonen  ist,  wird  hier  nur  von  einer  allgemeinen 
Herzschwache  geredet;  eine  auf  den  linken  Ventrikel  beschrankte  Schwachung 
wiirde  selbstverstandlich  die  Entstehung  von  Lungenodem  im  gegebenen  Falle 
erleichtern. 


20        ZUR  PATHOLOGIE  DES  LUNGENODEMS 

sind,  ist  karnii  anders  zu  erklaren  als  dadurch,  dass  die  Kraft  des  rechten 
Ventrikels  zu  gering  ist,  uin  die  notliige  Blutmasse  in  die  Lungen  hinein- 
zuschaffen.  Es  kann  auch  sein,  dass  die  Strorakraft  und  der  Gefasstonus 
gleichzeitig  so  herabgesetzt  sind,  dass  keine  geniigende  Blutmasse  in  die 
Venen  und  in's  rechte  Herz  hineinfliesst.  Ich  mochte  aber  bezweifeln,  dass 
eine  fiir  die  Entstehuug  von  Lungenodem  hinreichende  Blutmasse  nicht 
zur  Verfiigung  des  rechten  Ventrikels  stehe,  da  in  einem  almlichen  Ver- 
suclie,  in  welchem  der  Druck  in  der  Arteria  pulmonalis  durch  die  Unter- 
bindung  wenig  beeinflusst  war,  der  Druck  in  der  Vena  jugularis  von  0 — 10 
bis  zu  60  Mm.  Soda  stieg. 

In  gleichem  Sinne  spricht  ein  versuch  an  einem  Kaninchen  bei  welchem 
gleich  nach  Unterbindung  der  Aorta  zwischen  Truncus  anonymus  und 
linker  Subclavia  und  des  Truncus  anonymus  z%vischen  linker  und  rechter 
Carotis  der  Carotisdruck  von  100  Mm.  bis  zu  40  Mm.  Hg.  sank,  anstatt, 
wie  gewohnlich,  um  das  Zweibis  Dreifache  zu  steigen.  Dieser  ist  der  ein- 
zige  Falls  aus  zahlreichen  Versuchen,  bei  welchem  die  Unterbindung  der 
Aorta  und  ihrer  Aeste  an  einem  Kaninchen  nicht  starkes  Lungenodem  hervor- 
rief,  und  wir  haben  den  besten  Beweis  durch  das  Verhalten  das  Carotisdrucks, 
dass  die  plotzliche  Unt^rbrechmig  des  Blutstroms  eine  Herzlahmung 
bewirkte.  Hier  war  ein  holier  Druck  vorhanden,  als  die  Arterien  unter- 
bmiden  wurden,  so  dass  wir  das  Ausbleiben  von  Limgenodem  in  diesem 
Falle  ausschliesslich  der  geschwachten  Kraft  des  rechten  Ventrikels  zuschrei- 
ben  miissen,  wiihrend  die  Stromkraft  mid  der  Gefasstonus  zur  Zeit  der 
Unterbindung  normal  waren.  Uebrigens  sei  hier  erwahnt,  dass  dies  der 
einzige  Fall  war,  wo  eine  plotzliche  Herzlahmung  die  Folge  der  Unterbin- 
dung der  Aorta  war. 

Das  Verhalten  des  Herzens  nach  Unt^rbrechung  des  Kreislaufs  durch 
Verschliessung  der  grossen  Arterien  ist  nicht  ohne  Interesse.  Es  fiihrt 
nehmlich  bei  erhaltener  kiinstlicher  Athmung  oftmals  eine  Zeit  lang  fort 
mit  hohem  Drucke  zu  pulsiren.  Nachdem  der  grosse  Kreislauf  Stillstand 
gebracht  worden  ist,  kann  man  mit  einer  endstandigen  Manometercaniile 
in  der  linken  Carotis  und  einem  Sodamanometer  in  einem  Aste  der  Arteria 
pulmonalis  den  Druck  in  diesen  Gefassen  messen,  wahrend  das  Herz  die  var 
ilmi  stehonde  Blutsiiule  noch  kraftig  hin  und  her  treibt.  Die  Arterien 
werden  wie  in  Versuch  -i  zugebunden.  Wie  aus  diesem  Versuch  ersichtlich 
ist,  bleibt  der  Druck  eine  Zeit  lang  hocli ;  bei  Hunden  kann  er  sogar  noch 
eine  halbe  l)is  eine  Stuiule  eine  betrachtliche  Hohe  behaupten.  Um  sicher 
zu  sein,  dass  aller  Blut^uiluss  ausgeschlossen  sei,  habe  ich  nach  einiger 
Zeit  die  beiden  Hohlvenen  unterbunden,  ohne  das  Versuchsresultat  dadurch 
zu  voriindern.     Der  Puis  zeigt  die  oft  erwahnten,  grossen,  rhythmischen, 


ZUE  PATHOLOGIE  DES  LUNGllN'ODEMS  21 

periodischen  Schwankungen,  der  Druck  sinkt  sehr  allmahlich  und  nicht 
ganz  regelmassig,  sondern  erliebt  sich  von  Zeit  zn  Zeit. 

Eine  interessante  Frage  ist,  ob  unter  diesen  Verhaltnissen  der  Coro- 
narkreislauf  noch  existirt.  Als  Beweise  fiir  seine  Existenz  erwahne  ich  das 
Eolgende.  Ich  habe  mehrmals  beobachtet,  dass,  wenn  die  kiinstliche  Ath- 
mung  unterbrochen  wird,  nach  3 — 4  Minuten  der  Druck  anfangt  zu  sinken 
und  zwar  rascher  sinkt  als  bei  Fortsetzung  derselben.  Nach  Herstellung 
der  kiinstlichen  Athmung  steigt  er  wieder,  aber  diese  Steigerung  fangt  nicht 
gleieh  nach  Beginn  der  Athmung  an.  In  eineni  Versuche  an  einem  Hunde, 
nachdem  der  Carotisdruck  von  170  bis  zu  80  bei  sistenter  kiinstlicher  Respi- 
ration gesunken  war,  hat  er  seine  friihere  Hohe  nach  Herstellung  der 
kiinstlichen  Athmung  wieder  erreicht.  Bei  einem  Kaninchen,  an  dem 
der  grosse  Kreislauf  unterbrochen  war,  habe  ich  beobachtet,  dass  nach 
Einstellung  der  kiinstlichen  Athmung  das  Blut  im  Vorhofe  und  der  Coro- 
nararterien  allmahlich  dunkel  wurde,  und  dass  die  xAthmung  die  rothe 
Farbe  wieder  hervorrief.  Man  konnte  vielleicht  glaubeu,  dass  das  Missver- 
haltniss  zwischen  der  Blutmenge  und  dem  Gefassrauminhalt  unter  diesen 
Umstanden  so  gross  sei,  dass  der  Blutdruck  iiberhaupt  nicht  auf  Null 
sinken  wiirde,  das  ist  aber  nicht  der  Fall. 

Ein  Saugethierherz,  welches  so  machtig  miter  dem  Reize  des  hohen 
Blutdrucks  fiir  eine  halbe  bis  eine  Stunde  pulsirt,  bei  welchem  die  Kraft 
der  Systole  durch  Druckmesser  ermittelt  werden  kann,  bei  welchem  cen- 
trales Nervensystem  und  Gefasstonus  ausser  Wirkung  gesetzt  sind,  und  bei 
dem  der  Coronarkreislauf  noch  existirt,  ware  kein  unwiirdiger  Gegenstand 
fiir  weitere  Unter suchungen.  Die  Dauer  und  die  einzelnen  Phasen  des 
Phanomens  sind  variabel,  aber  die  Bedingungen  derselben  habe  ich  nicht 
weiter  verfolgt.  Hunde  sind  am  besten  fiir  die  Beobachtung  derselben 
geeignet.  Bei  Kaninchen  scheint  es  am  vortheilhaftesten,  die  Gefasse  in 
der  folgenden  Reihe  zu  unterbinden,  die  Aorta  zwischen  Truncus  anony- 
mus  und  linker  Subclavia,  die  untere  Hohlvene  im  Thorax,  der  Truncus 
anonym  us  dicht  peripher  von  linker  Subclavia  (Hg.-Manometer  in  linker 
Subclavia).  Wenn  man  bei  einem  Kaninchen  die  aufsteigende  Aorta 
zubindet,  pulsirt  der  linke  Ventrikel  gewohnlich  nicht  lange  fort  und  das 
Herz  steht  weit  mit  Blut  ausgedehnt  still.  Nicht  selten  habe  ich  kleine 
Blutungen  unter  dem  Visceralblatt  des  Pericards  nach  Unterbindung  der 
Aorta  beobachtet. 

Da  wir  bisher  nur  die  Erzeugung  von  Limgenodem  durch  Stromhinder- 
nisse  im  grossen  Kreislauf  besprochen  haben,  so  bleibt  noch  iibrig,  die  Ent- 
stehung  desselben  in  Folge  von  vermehrten  Widerstanden  im  kleinen  Kreis- 
lauf selbst  und  im  linken  Abschnitte  des  Herzens  zu  betrachten. 


22       ZUK  PATHOLOGIE  DES  LUNGENODEMS 

Um  die  Lungenvenen  zu  unterbinden  macht  man  ein  Eenster  im  Thorax, 
wie  fiir  Druekmessung  an  der  Lungenarterie.  Beim  Kaninchen  sind 
gewohnlich  zwei  Venenaste,  beim  Hunde  drei  der  linken  Lunge,  deren 
Unterbindung  keine  sonderliche  Schwierigkeit  bietet.  Beim  Kaninchen  ist 
es  rathsam,  ohne  kiinstliche  Athmung  zu  operiren,  da  die  Lunge  dann 
zusammengefallen  ist,  aber  man  muss  sich  in  Acht  nehmen,  bei  der  Umle- 
gung  eines  Fadens  um  den  unteren  Venenast,  nicht  die  Pleura  der  rechten 
Seite  zu  verletzen,  weil  dies  die  Anwendung  der  kiinstlichen  Athmung 
sogleich  unabweislich  maeht.  Die  Venenaste  zu  dem  oberen  und  dem 
mittleren  Lappen  der  rechten  Lunge  sind  leicht  zu  erreichen,  aber  der  Ast 
zu  dem  unteren  Lappen  imd  besonders  der  zu  dem  zungenformigen  hinter 
der  unteren  Hohlvene  liegenden  Lappen  sind  nur  mit  grosser  Schwierig- 
keit zu  fassen,  so  dass  ich,  wenn  es  darauf  ankam  sammtliche  Lungenvenen 
zu  unterbinden,  es  vorgezogen  babe,  die  AVurzel  der  rechten  Lunge  entweder 
im  Ganzen  oder  in  ihrem  unteren  Theile  en  masse  zuzubinden,  wodurch 
natiirlich  in  dem  betreffenden  Theile  der  arterielle  Zufluss  abgeschlossen 
wird,  was  nach  den  Untersuchungen  von  Lichtheim  die  Blutmasse  in 
den  freien  Theilen  vermehren  muss.  Sowohl  wenn  man  seine  Wurzel  en 
masse  unterbinden  will,  als  wenn  man  seine  Vene  sucht,  ist  es  nothig  diesen 
zungenformigen  Lappen  hinter  der  Vena  cava  herauszuziehen  und  eine 
Art  von  Ligamentum,  welches  sein  Pleurafortsatz  bildet,  mit  den  Fingern 
sorgfaltig  zu  zerreissen,  was  sich  ohne  Blutung  ausfiihren  lasst. 

Wie  schon  erwiihnt,  bedingt  die  Verschliessung  sammtlicher  Venen  der 
einen  Lunge  kein  Oedem.  Das  Thier  lebt  mehrere  Stunden  nach  der  Opera- 
tion und  nach  dem  Tode  findet  man  die  betreffende  Lunge  vollstandig 
hamorrhagisch  infarcirt.  Im  Gegensatz  zu  dem  Auftreten  von  Lungen- 
odem  braucht  es  eine  verhiiltnissmassig  geraume  Zeit,  ehe  diese  Infarcirung 
zu  Stande  kommt,  wiihrend  das  Oedem  gleich  erscheint,  wenn  der  Blutab- 
fluss  hinreichend  gehemmt  wird.  Wenn  ausser  den  Venen  der  linken  Lunge, 
die  Venen,  welche  von  dem  oberen  und  dem  mittleren  rechten  Lappen 
kommen,  zugcbunden  werden,  bleibt  auch  das  Lungenodcm  aus.  In  der 
That  muss  man  den  Abflussweg  aus  den  Lungen- 
venen fast  vollstandig  verlegen,  ehe  es  zur  serosen 
Ausschwitzungkommt.  So  lange  ein  Ast  zweiter  Ordnung  offen 
bleibt,  ist  das  Hinderniss  noch  nicht  gross  genug.  Kaninchen  und  Hunde 
verhalt^n  sich  in  dieser  Beziehung  ungefahr  gleich. 

Versuch  5.  Mittelgrosser  curarisiter  Hund.  Hg.-Manometer  in 
Verbindung  mit  linker  Carotis.  Druck  60—70.  Soda-:Manometer  im 
unteren  Aste  der  linken  Lungenarterie.  Druck  120.  Xach  Unterbindung 
des  Hilus  der  recliten  Lunge  bleibt  der  Carotisdruck  unveriindert,  wahrend 
der  Pulmonaldruck  bis  zu  300  steigt.    Gleich  danach  werden  die  Venen  der 


ZUR  PATHOLOGIE  DES  LUNGENODEMS       23 

linken  Lunge,  mit  Ausnahme  eines  kleinen  Astes  der  unteren  Vene,  unter- 
brniden.  Der  Carotisdruck  sinkt  auf  40  Mm.,  wo  er  5 — 6  Mimiten  unver- 
andert  bleibt,  und  sinkt  dann  welter.  Ein  Hg.-Manometer,  welcher  anstatt 
des  zu  niedrigen  Soda-Manometers  in  Verbindung  mit  demselben  Aste  der 
Lungenarterie  gesetzt  worden  ist,  zeigt  eine  Druckhohe  von  55  Mm.  Hg.  in 
Folge  der  Venenunterbindung.  Die  Obduction  ergiebt  selir  starke  Stauung 
nnd  Oedem  der  linken  Lunge ;  rechte  Herzhalfte  ausgedehnt,  linke  fast  leer. 
Einspritzung  von  chromsaurem  Blei  in  den  linken  Vorhof  zeigt,  dass  alle 
die  Gefasse,  wie  oben  angegeben,  fest  verschlossen  sind  und  dass  nur  ein 
kleiner  Ast  des  linken  unteren  Venenstammes  offen  bleibt. 

Unterbindung  sammtlicher  Lungenveneri,  so  dass  aller  Abfluss  aus 
denselben  so  plotzlich  wie  moglich  aufhort,  ist  weniger  giinstig  fiir  das 
Zustandekommen  von  Lungenodem,  als  wenn,  wie  in  dem  eben  bescbriebenen 
Versuche,  ein  sehr  geringes  Ausfliessen  in  den  linken  Ventrikel  ermoglicht 
wird.  Nach  Verschliessung  sammtlicher  Lungenvenen  stirbt  das  Thier 
ausserst  rasch  und  das  Herz  pulsirt  nachher  nur  kurze  Zeit.  Bei  vier  Ver- 
suchen  an  Kaninchen  verursachte  die  Unterbindung  der  Lungenvenen  (i,  e. 
der  Wurzel  der  rechten  Lunge  und  sammtlicher  Venen  der  linken)  zweimal 
Lungenodem. 

Versuch  6.  Starkes  Kaninchen.  Tracheotomie.  Druck  in  rechter 
Carotis  100 — 115  Mm.  Hg.  Faden  um  die  beiden  Venen  der  linken  Lunge 
gelegt.  Kiinstliche  Athmung.  Unterbindung  der  ganzen  Wurzel  der 
rechten  Lunge.  Carotisdruck  bleibt  unverandert.  Gleich  nachher  die 
beiden  linken  Lungenvenen  zugebunden.  Carotisdruck  sinkt  gleich  auf  Null. 
In  10  Secunden  nach  vollendeter  Unterbindung  wird  das  Thier  unruhig, 
in  20  Secunden  bekommt  es  heftige  Krampfe  und  in  45  Secimden  ist  es 
todt.  Die  sofortige  Obduction  ergiebt  deutliches,  aber  nicht  starkes  Oedem 
der  linken  Lunge.  Beide  Lungen  hyperamisch,  die  rechte  dunkelroth,  die 
linke  hellroth.  Eechte  Herzhalfte  stark  ausgedehnt,  linker  Ventrikel  leer, 
zusammengezogen.     Korpervenen  gestaut. 

Verengerung  der  Venenbahn  der  Lunge  scheint  den 
Carotisdruck  ebensowenig  herabzusetzen  wie  die  Verschliessung  ent- 
sprechender  Abschnitte  der  Lungenarterien.  Man  kann  die  Lungenvenen 
wenigstens  bis  zu  drei  Viertel  ihrer  Capacitat  verschliessen,  ohne  dass  der 
Carotisdruck  wesentlich  beeinflusst  wird,  aber  nach  Ueberschreitung  einer 
gewissen  Grenze  fangt  der  Druck  im  Aortensystem  an  zu  sinken. 

Der  Druck  in  der  Pulmonalarterie  steigt  weniger  nach  Unterbindung 
von  Aesten  der  Lungenvenen  als  nach  Verschliessung  entsprechender 
Arterien. 

Versuch  7.  Grosser,  curarisirter  Hund.  Druck  in  linker  Carotis 
100 — 120  Mm.,  im  unteren  Aste  der  Art.  pulmonalis  sinistra  20  Mm.  Hg. 
Zubindung  der  drei  linken  Lungenvenen  bewirkt  Veranderung  weder  im 
Carotis-  noch  im  Pulmonalisdruck.  Unterbindung  der  Venen,  welche  von 
dem  oberen  und  dem  mittleren  rechten  Lappen  herkommen,  hat  keinen 


24        ZUK  PATHOLOGIE  DES  LUNGEXODEMS 

Einfluss  auf  den  Carotisdruck,  aber  der  Druck  in  der  Art.  pulmonalis  steigt 
4  Mm.  Es  bleibt  jetzt  bios  die  Vene  offen,  allerdings  eine  grosse,  welche  von 
dem  rechten  miteren  Lappen  herkommt.  Die  Wurzel  der  rechten  Lunge 
wird  en  masse  fest  zugebunden.  Der  Druck  in  der  Carotis  sinkt  gleich  fast 
auf  Null;  der  Pulmonalisdruck  steigt  fiir  einen  Augenblick  rasch,  sinkt 
dann  plotzlich  und  das  Herz  steht  still  und  lost  keine  Contraction  mehr  aus. 
Die  Obduction  zeigt  beide  Lungen  blutreich,  aber  kein  Oedem.  Einspritzung 
mit  ehromsaurem  Blei  ergiebt,  dass  bei  der  Unterbindung  der  Lungenwurzel 
nur  der  Venenstanmi  des  rechten  unteren  Lappens  offen  geblieben  war. 

Der  plotzliche  Herzstillstand,  welcher  der  Zubindung  der  rechten  Lungen- 
wurzel  in  diesem  Falle  folgte,  erklart  zur  Geniige  das  Ausbleiben  von  Lun- 
genodem.  Wie  schon  oben  erwiihnt,  tritt  oft  unmittelbar  nach  Unterbindung 
der  Venen  der  einen  Lunge  und  der  Wurzel  der  anderen,  wenn  nicht  eine 
vollstandige  Paralyse,  so  doch  eine  deutliche  Schwachung  des  Herzens  ein. 
Eine  Parese  des  rechten  Yentrikels  aber,  wie  wir  sie  bei  Unterbindung  der 
Aorta  schon  gefunden  haben,  ist  ein  ungiinstiger  Zu^tand  im  Betreff  des 
Zustandekommens  von  Lungenodem,  obwohl  sie  einen  betrachtlichen  Grad 
erreichen  muss,  ehe  die  Entstehung  des  Lungen odems  verhindert  wird. 

Ist  die  Herzlahmung,  welche  in  einigen  Fallen  beobachtet  wurde,  die 
Folge  des  plotzlichen  Verschlusses  des  Ausfliessens  aus  den  Lungenvenen, 
wobei  der  Coronarkreislauf  zuni  Stillstand  gebracht  wird  (im  Gegensatz 
zur  L^nterl)indung  der  Aorta,  S.  23),  oder  die  Folge  der  langdauemden  und 
tiefeingreifenden  Operation?  Die  Eroffnung  beider  Pleurahohlen,  die 
imvermeidliche  Storung  und  Zerrimg  der  dem  Herzen  anliegenden  Gebilde, 
die  Beriihrung  und  Verschiebung  des  Herzens  selbst  bei  Zubindung  der 
tiefliegenden  unteren  und  hinteren  Venen  der  rechten  Lunge  oder  der  Lun- 
genwurzel,  und  die  lange  Dauer  der  Operation  beim  Lufteintritt  in  die 
Pleurahohlen  sind  alles  Momente,  welche  wohl  die  Herzkraft  bedeutend 
herabsetzen  konnen.  Beutner**  hat  darauf  aufmerksam  gemacht,  dass 
bei  offoner  Pleuraliiihle  die  rechte  Herzkraft  sich  bedeutender  abschwacht 
als  die  linke,  dass  die  erstere  im  Sinken  begriffen  sein  kann,  wahrend  die 
letztere  noch  steigt.  Eine  mogliche  Erklarung  findet  er  darin,  „  dass  das 
linke  Herz  sich  weniger  leicht  abkiihlt  wegen  seiner  dickeren  Muskelmasse  ". 
Fiir  uus  liegen  die  Verhaltnisse,  wie  wir  sehen  werden,  gcrade  umgekehrt: 
Schwachung  des  linken  Ventrikels  bei  so  wenig  wie  moglich  beeintriichtigter 
Kraft  des  rechten  Ventrikels  ist  es,  welche  die  Entstehung  von  Lungenodem 
begiinstigt.  Desshalb  sind  die  bei  Unterbindung  der  Lungenvenen  noth- 
wendigen  Eingriffe  fiir  unseren  Zweek  direct  entgegenwirkender  Natur.  Die 
Versuche  von  B  e  z  o  1  d  "  iiber  Zuklemmung  der  Kranzarterien  erlauben  uns 

"  Ueber  die  Strom-  und  Druckkrafte  des  Blutes  in  der  Arteria  und  Vena  pul- 
monalis.    Zeitschrift  fiir  rat.    Med.   N.   F.   Bd.  2,   S.   119.     1852. 
"  Untersuch.  aus  d.  physiol.   Laborat.   in  Wiirzburg.   1867.  Hft.   2. 


ZUR  PATHOLOGIE  DES  LUNGENODEMS       25 

auch  nicht  dem  Aufhoren  des  Coronarkreislaufs  alien  Einfluss  abzusprechen, 
mn  so  mehr  da  beim  Einfliessen  einer  sehr  kleinen  Blutmenge  Lungenodem 
leichter  zu  Stande  kommt,  als  bei  vollstandiger  Abspeming  der  Blutzufuhr 
Yom  linken  Ventrikel. 

Das  fiir  unsereu  Zweck  wichtigste  Ergebniss  der 
Versuche  iiber  Einsetzung  von  Hindernissen  in  den 
Abfluss  des  Blutes  aus  den  Lungenvenen  in  den 
linken  Ventrikel  ist,  dass  dadurch  zwar  Lungenodem 
erzeugt  werden  kann,  dass  aber  diese  Hindernisse 
enorm,  ja  dass  fast  sammtliche  Lungenvenenaste 
verlegt  werden  miissen,  ehe  Oedem  entsteht,  und 
dass  erst  bei  diesen  colossalen  Widerstanden  der 
Druck  in  der  P  ul  m  o  n  a  1  a  r  teri  e  eine  bedeutende 
Steigerung  erleidet. 

Demjenigen,  der  mit  Untersuchungen  iiber  den  Lungenkreislauf  nicht 
naher  vertraut  ist,  kann  es  vielleicht  auffallen,  dass  ich  mir  Schliisse  iiber 
den  Druck  in  den  Lungenvenen  aus  Messungen  in  der  Lungenarterie  erlaubt 
habe,  Alle  Forscher  "  aber,  welche  Druckmessungen  in  den  Lungengefassen 
angestellt  haben,  stimmen  darin  iiberein,  dass  die  Widerstande  in  den 
Lungencapillaren  so  klein  sind,  dass  Druckerhohung  in  den  Lungenvenen 
von  einer  gleichsinnigen  Veranderung  in  der  Lungenarterie  begleitet  ist. 
Die  Untersuchungen  von  Lichtheim  haben  es  wahrscheinlich  gemacht, 
dass  der  Tonus  der  Lungengefasse  ausserst  gering  ist.  B  e  u  t  n  e  r  f and  bei 
einer  Katze  9  Mm.  Hg.  als  Maximalwerth  der  Differenz  der  Druckkriifte  in 
der  Arterie  und  in  der  Vene  am  Vorhofe.  Wir  aber  sind  bei  unseren  Unter- 
suchungen um  so  mehr  berechtigt,  von  dem  Druckwerthe  in  der  Lungenar- 
terie einen  Schluss  auf  die  relative  Spannung  in  der  Vene  zu  ziehen,  als  es 
sich  um  ganz  grobe  Abweichungen  von  der  Norm  handelt. 

Weniger  well  es  von  principieller  Bedeutung  ist,  als  um  alle  Wege  zu 
untersuchen,  auf  welchen  mechanische  Hindernisse  den  Abfluss  des  Blutes 
aus  der  Lunge  hemmen  konnen,  habe  ich  bei  Kaninchen  durch  Abbindung 
des  grossten  Theiles  des  linken  Vorhofes  und  durch  Zuklemmung  des  linken 
Ventrikels  Lungenodem  zu  Stande  gebracht.  Es  ist  erstaunlich,  ein  wie 
grosser  Abschnitt  des  Vorhofes  oder  des  Ventrikels  verlegt  werden  muss, 
nicht,  nur  ehe  Lungenodem  eintritt,  sondern  auch  ehe  der  Carotisdruck  zu 
sinken  anfangt.  Ich  mochte  sagen,  dass  wenigstens  drei  Viertel  der 
Capacitat  des  linken  Ventrikels  ausgeschaltet  werden  miissen,  um  Lungen- 
odem zu  verursachen.  Die  Zuklemmung  geschah  mit  stark  federnden,  breiten 
Charriere'schen  Klemmpincetten.    In  einem  Versuche  lebte  das  Thier  eine 

=*Beutner,G.  Colin,  Badoud.Hofmokl,  Lichtheim. 
5 


26        ZUR  PATHOLOGIE  DES  LUNGENODEMS 

halbe  Stunde,  nachdem  wenigstens  die  Halfte  des  linken  Ventrikels  zuge- 
klemmt  war  und  starb  mit  Erstickungserscheimmgen  ohne  Lungenodem. 
Die  erste  Wirkung  einer  partiellen  Zuklemmung  besteht  darin,  durch  Herz- 
reizung  (oder  durch  Hirnanamie  ?)  den  Druck  in  der  Art.  earotis  zu  erhohen, 
welcher  auch  nach  Abnahme  der  Klemmpincetten  hoch  bleibt.  In  einem 
Versuche  habe  ich  beobachtet,  dass,  gleieh  nachdem  der  grosste  Theil  des 
linken  Ventrikels  zugeklemmt  wnrde,  das  Thier  in  einen  tetanischen  Zustand 
gerieth.  Dasselbe  wurde  bewusstlos  und  blieb  unerregbar  bis  zum  Tode, 
welcher  (durch  Drucksinkung  erkennbar)  nach  ungefahr  15  Minuten  ohne 
Ivrampfe  oder  Dyspnoe,  aber  mit  starkem  Lungenodem,  eintrat. 


Nachdem  wir  die  Bedingungen  ermittelt  haben,  unter  welchen  ein 
mechanisches  Oedem  der  Lunge  an  Kaninchen  und  Hunden  experimentell 
lierbeizuf iihren  ist,  so  entsteht  die  Frage :  welches  Licht  werfen  die  vorliegen- 
den  Beobachtungen  auf  die  Ursachen  des  Lungenodems  beim  Menschen? 
Es  liegen  gewiss  die  Bedingungen  des  Lungenodems,  welches  ich  durch 
mechanische  Momente  zu  Stande  gebracht  habe,  sehr  weit  entfemt  von  den- 
jenigen,  welche  in  der  grossten  Mehrzahl  der  Falle  von  acutem,  allgemeinem 
Hydrops  pulmonum  beim  Menschen  herrschen,  und  iiber  die  Entstehung  des 
letzteren  konnen  die  Ergebnisse  der  oben  erwahnten  Versuche  anscheinend 
wenig  Positives  aussagen.  Und  doch  liegt,  meiner  Meinung  nach,  in  ihnen 
der  Schliissel  zur  Losung  des  Problems,  das  uns  beschaftigt. 

Das  Oedem,  welches  ich  kiinstlich  erzielt  habe,  ist  ein  Stauungsodem  und 
tritt  erst  dann  ein,  wenn  der  Druck  im  Lungenkreislauf  bedeutend  erhoht 
ist.  Das  mikroskopische  Bild  dieses  Oedems  stimmt  in  alien  seinen  wesent- 
lichen  Charakteren  mit  dem  des  allgemeinen  Lungenodems  deim  Menschen 
iiberein.  Bei  beiden  sieht  man  hochgradige  Fiillung  der  Lungencapillaren 
und  zalilreiche  ausgetretene  rothe  Blutkorperchen.  Diese  Uebereinstimmung 
bestiirkt  an  sich  die  ohne  geniigende  Griinde  gewohnlich  angenommene  An- 
sicht,  dass  das  Lungenodem  ein  Stauung&odem  sei.  Indess  haben  die 
obigen  Versuche  die  gelaufigen  Erklarimgen  dieses  Oedems  entkraftigt.  Von 
denselben  giebt  es  eigentlich  nur  zwei,  welche  Anspruch  auf  Wahrschein- 
lichkeit  machen  konnen  und  in  Einklang  mit  klinischen  Erfahrungen  zu 
stehen  scheinen.  Dies  sind  die  beiden  oben  angegebenen  Ursachen  der 
venosen  Stauung,  Storung  des  Abflusses  des  Blutes  aus  den  Pulmonalvenen 
durch  Klappenfehler  des  linken  Ventrikels  und  geschwachte  Herzaction. 
Es  fehlt,  meiner  Ansicht  nach,  ohnehin  nicht  an  Griinden,  imi  die  Unzu- 
langlichkeit  beider  Momente  fiir  die  Erklarung  des  Zustandekommens  des 
Oedema  pulmonum  nachzuweisen ;  jedenfalls  lassen  die  Ergebnisse  des  Ex- 
periments ihre  Unhaltbarkeit  klar  zu  Tage  treten.  Eine  „  Storung  des 
Abflusses  des  Blutes  aus  den  Pulmonalvenen  "  durch  mechanische  Hinder- 


ZUE  PATHOLOGIE  DES  LUNGENODEMS        27 

nisse  verursacht  erst  dann  Oedem  der  Lunge,  wenn  dadurch  fast  sammtliche 
Venenaste  verlegt  worden  sind.  Von  solchen  Hindernissen  im  grossen  oder 
im  kleinen  Kreislauf  kann  beim  Menschen  kaum  die  Rede  sein ;  wenigstens 
miissen  wir  diesem  Momente  eine  allgemeine  Bedeutung  bei  der  Losung 
unseres  Problems  absprechen,  Geschwachte  Action  des  ganzen  Herzens 
erzeugt  nicht  nur  an  und  fiir  sich  kein  Oedem,  sondern,  wenn  selbst  die  son- 
stigen  Bedingungen  vorhanden  sind,  kann  sie  das  Auftreten  desselben 
hintanhalten. 

Giebt  es  denn  keine  andere  Ursache  fiir  Lungenstauung,  welche  wir  als 
die  Bedingung  von  Lungenodem  betrachteri  konnen,  ohne  mit  den  bekannten 
Eigenschaften  der  Pulmonalcirculation  und  den  klinischen  Beobaehtungen  in 
Widerspruch  zu  treten?  Oder  sollen  wir  etwa  auf  die  Wirkung  mechan- 
ischer  Momente  verzichten  und  unsere  Zuflucht  zu  der  Annahme  einer 
unbekannten  Gefasswandveranderung  nehmen  ?  Zu  solch  einem  Schritt  wird 
sich,  denke  ich,  schwerlich  jemand  entschliessen,  so  lange  nicht  alle  mechan- 
ischen  Erklarungsmoglichkeiten  erschopft  sind.  Eine  solche  aber  scheint 
mir  jedes  Missverhaltniss  zwischen  der  Ej*aft  des  linken  und  der  des  reehten 
Ventrikels  zu  sein,  wobei  der  erstere  nur  einen  Bruchtheil  der  Blutmenge 
in  der  Zeiteinheit  heraustreiben  kann,  welche  der  letztere  in  die  Lungenar- 
terie  hineinschafft,  d.  h.  eine  linksseitige  Lahmung  des 
Herzens. 

Wenn  ich  das  Wort  Missverhaltniss  gebrauche,  so  denke  ich  selbstverstand- 
lich  nicht  an  den  absoluten  Unterschied  zwischen  der  Kraft  des  reehten  und 
der  des  linken  Ventrikels.  Diese  Kraft  steht  bekanntlich  in  directem 
Verhaltnisse  mit  der  Widerstandshohe  am  Anfang  des  grossen  resp.  des 
kleinen  Kreislaufs.  Die  Triebkraft  des  linken  Ventrikels  kann  bedeutend 
vermindert  werden,  wahrend  die  des  reehten  unverandert  bleibt  oder  sogar 
erhoht  wird,  oline  dass  ein  Missverhaltniss  zwischen  denselben  sich  ausbildet, 
vorausgesetzt,  dass  die  Widerstande  im  gleichen  Sinne  und  in  demselben 
Verhaltnisse  sich  andern.  Ein  solch  relatives  Missverhaltniss 
zwischen  der  arbeitskraft  des  linken  Ventrikels  und  der  des  reehten  bedeutet 
dagegen,  dass  bei  gleichbleibenden  Widerstanden  das 
linke  Herz  nicht  dieselbe  Blutmenge  in  der  Zeit- 
einheit   hinauszutreiben   vermag,    wie    das   rechte. 

Gesetzt  den  Fall,  der  linke  Ventrikel  wird  gelahmt,  der  rechte  arbeitet  mit 
unverminderter  Kraft  fort  und  empfangt  nicht  weniger  Blut  als  vorher,  was 
muss  geschehen  ?  Das  Blut  muss  sich  in  den  Lungengefassen  haufen,  bis  der 
beharrliche  Zustand,  der  bei  jedem  Kreislaufe  eine  Nothwendigkeit  ist, 
eintritt.  Dieser  kommt  erst  dann  zu  Stande,  wenn  die  Widerstandshohe  in 
der  Lungenarterie  so  gross  geworden  ist,  dass  der  rechte  Ventrikel  nur 
dieselbe  Menge  Blut  in  der  Zeiteinheit  hineintreiben  kann,  wie  aus  den 


28        ZUR  PATHOLOGIE  DES  LUNGENODEMS 

Lungenvenen  herausfliesst.  Es  ist  klar,  dass  je  schwacher  der  linke  Ventrikel 
einerseits  und  je  starker  der  rechte  andererseits,  desto  grosser  die  Druckhohe 
in  dem  Lungenkreislauf  ausfallen  wird,  bei  welcher  der  beharrliche  Zustand 
entsteht. 

Ob  diese  Druckerholmng  in  einem  gegebenen  Falle  Lnngenodem  verur- 
sacben  wird,  ja  ob  sie  iiberhaupt  dazu  hinreicht,  ist  von  vornherein  nicht  mit 
Bestimmtbeit  zu  sagen.  Es  bedarf  keiner  Erorterung,  dass  die  dynamischen 
Momente  andere  sind  als  bei  mecbauischen  Hindemissen  fiir  den  Abfluss  des 
Blutes  aus  den  Lungenvenen,  wo  eine  geringe  Drucksteigening  geniigt, 
um  erbeblicbe  Widerstiinde  zu  iiberwinden.  Selbst  wenn  ich  keine 
experimentellen  Beweise  dafiir  beibringen  konnte,  dass  eine  linksseitige 
Herzschwaehung  ausreicht  um  Lungenodem  zu  erzeugen,  so  glaube  ich  doch 
in  Ansicht  der  ]\Iangelbaftigkeit  anderer  Tbeorien,  dass  es  nicht  unniitz 
ware  auf  diese  Hypothese  aufmerksam  zu  machen,  welche  uns  wenigstens 
eine  sebr  plausible  Erklarung  der  Entstehung  von  Lungenodem,  im  Wider- 
spruch  weder  mit  den  bekannten  Eigenschaften  der  Pulmoualcirculation 
noch  mit  der  klinischen  Beobachtung,  darbietet.  Selbstverstiindlich  aber 
muss  die  Hypothese  eine  ganz  andere  Stellung  gewinnen,  wenn  es  sich 
beweisen  liesse,  dass  eine  linksseitige  Herzschwaehung  an  und  fiir  sich  geniigt 
um  Lungenodem  zu  Stande  zu  bringen,  und  deshalb  schien  es  geboten, 
dieselbe  einer  experimentellen  Priifung  zu  unterwerfeu. 

Durch  welche  Mittel  aber  ist  es  moglich  eine  einseitige  Herzliibmung  zu 
erzeugen  ?  Unter  den  vcrschiedenen  Herzgiften  hat  keines,  so  viel  mir 
bekannt,  die  Eigenschaft  allein  oder  hauptsachlich  auf  den  einen  Ventrikel 
zu  wirken.  Die  Kalisalze,  Jodsalze,  Kohlenoxyd,  Strychnin  konnen  alle  als 
eine  inconstante  Folge  ibrer  giftigen  Wirkung  Lungenodem  herbeifiihren. 
Aber  wegen  der  Inconstanz  dieser  Erscheinung  und  wegen  der  Schwierig- 
keit  einen  Beweis  zu  liefern,  dass  in  einem  gegebenen  Falle  der  eine  Ven- 
trikel starker  afficirt  sei  als  der  andere,  musste  ich  bald  voni  Experimen- 
tircn  mit  den  Herzgiften  absehen.  Wenn  nach  dem  Tode  der  rechte  Ven- 
trikel sich  zusammenzieht,  wiihrend  der  linke  stillsteht,  os  ist  dieses  kein 
Beweis,  dass  der  letztere  gelahmt  gewesen  ist,  da  bekanntlich  bei  alien  abster- 
benden  Herzen  das  rechte  Herz  seine  Coutractionsfahigkeit  liinger  bewahrt 
als  das  linke,  und  Du  Bois  Reymond  gezeigt  hat,  dass  der  kraftigere 
^fuskol  seine  Reizbarkcit  rascher  einbiisst  als  der  weniger  reizbare. 

Auch  die  locale  Einwirkung  schiidlicher  Stoffe  auf  die  Aussenflache  des 
linken  Ventrikels  erwies  sich  als  fiir  unseren  Zweck  vollig  ungeniigend. 
Ich  versuchte  durch  Aufstreuen  von  Kalisalzen,  durch  Aufgiessen  von 
Cliloroform,  durch  Eis,  durch  ITitze  die  Kraft  des  linken  Ventrikels  zu 
beeintriichtigen.  Er  zeigte  aber  eine  erstaunliche  Widerstandsfahigkeit.  Es 
gelang  mir  in  den  meisten  Fallen  nur  eine  starkere  Action  des  Herzens  und 


ZUE  PATHOLOGIE  DES  LUNGENODEMS       29 

erhohten  Carotisdruck  zu  erzielen,  und  wenn  einmal  der  linke  Ventrikel 
stillstand,  so  wurde  der  rechte  auch  niliig. 

Endlich  erreichte  ich  das  erwiinschte  Ziel  durch  Quetschimg  der  Wand 
des  linken  Ventrikels.  Fiir  diesen  Zweck  sind  die  Finder  das  beste  Instru- 
ment,  Pineetten  u.  s.  w.  zerreissen  die  Muskelwand  zu  leieht.  Ich  habe  den 
Eingriff  bios  am  Kaninchenherzen  gemacht,  da  das  Herz  des  Hiinds  zu 
starkwandig  und  kraftig  ist.  Der  linke  Ventrikel  wird  zwischen  den 
Daumen  und  einen  oder  zwei  Finger  genommen,  so  dass  so  viel  wie  moglich 
seiner  Muskelwand  inclusive  des  Septum  yentriculorum  gefasst  wird,  ohne 
den  recliten  Ventrikel  zu  beeintrachtigen,  und  dann  stark  zusammenge- 
drlickt.  Es  erfordert  eine  nicht  geringe  Kraft  um  den  Ventrikel  wlrklich 
zu  lahmen.  Ein  Hg.-Manometer  muss  in  Verbindung  mit  einer  Carotis 
stehen,  damit  man  die  Kraft  des  linken  Ventrikels  beurtheilen  kann.  Durch 
diese  Methode  habe  ich  in  vielen  Fallen  den  linken  Ventrikel  entweder  zum 
Stillstand  gebracht,  oder  mehr  oder  weniger  vollstandig  gelahmt,  wahrend 
der  rechte  noch  einige  Zeit  stark  pulsirt.  In  vielen  Fallen  aber  hatte  der 
Eingriff  andere  Wirkungen.  Nicht  selten  stand  das  ganze  Herz  plotzlich 
still,  selbst  nachdem  ein  verhaltnissmassig  geringer  Druck  auf  dasselbe  ausge- 
iibt  worden  war;  oft  wurden  beide  Ventrikel  gleichmassig  und  gleichzeitig 
geschwacht.  War  endlich  die  Quetsehung  nicht  stark  oder  nicht  ausgedehnt 
genug  ausf alien,  so  wirkte  haufig  der  Eingriff  als  ein  Reiz  fiir  den  Herz- 
muskel. 

Obwohl  ein  einziger  Fall  von  unzweideutiger  Lahmung  des  linken  Ven- 
trikels bei  Fortarbeiten  des  rechten  geniigt  hatte,  um  die  Moglichkeit  dieses 
Zustandes  zu  beweisen  und  die  Folgen  desselben  zu  beobachten,  suchte  ich 
doch  durch  ein  grosseres  Beobachtungsmaterial  die  daraus  gezogenen 
Schliisse  ausser  allem  Zweifel  zu  setzen,  Dabei  vnirden  viele  Thiere  nutzlos 
geopfert;  doch  ist  es  mir  gelungen  in  einer  grossen  Anzahl  von  Versuchen 
eine  deutliche  allein  oder  hauptsachlich  auf  den  linken  Ventrikel  beschrankte 
Lahmung  zu  erzielen,  und  ich  kann  mit  Bestimmtheit  behaupten,  dass  bei 
einer  gewissen  Kraft  des  rechten  Ventrikels  eine  hinreichend  hochgradige 
Schwachimg  des  linken  Lungenodem  herbeifiihrt. 

Versuch  8.  Mittelgrosses  Kaninchen.  Kiinstliche  Athmung. 
Quecksilberdruck  in  rechter  Carotis  100 — 120  Mm.  Thorax  in  der  Mittel- 
linie  geoffnet  und  das  Herz  durch  Eroffnung  des  Pericards  blossgelegt.  Der 
linke  Ventrikel  wird  zwischen  den  Fingem  stark  zusammengedriickt.  Der- 
selbe  steht  in  Contraction  absolut  still  und  lost  keine  erkennbare  Pulsation 
mehr  aus.  Der  Carotisdruck  sinkt  auf  20  Mm.  Der  rechte  Ventrikel,  der 
zuerst  stillstand,  fangt  nach  einigen  Secunden  an  wieder  zu  pulsiren  und 
zieht  sich  3  Minuten  lang  anscheinend  kraftig  und  in  regelmassigem  Ehyth- 
mus  zusammen.  Die  beiden  Vorhofe  pulsiren  ungefahr  dreimal  so  schnell 
als  der  Ventrikel.    Die  Arteria  pulmonalis  und  die  beiden  Vorhofe  werden 


30        ZUR  PATHOLOGIE  DES  LUNGEXODEMS 

stark,  der  rechte  Ventrikel  massig  ausgedehnt.  Xach  2 — 3  Minuten  bekommt 
das  Thier  Krampfe  und  stirbt.  Die  Obduction  ergiebt  sehr  starkes  Oedem 
beider  Lungen. 

Versuch  9,  Grosses  Kaninehen.  Kiinstliche  Athmung.  Druck  in 
linker  Carotis  90  ^Mm.  Hg.  Eroffnung  des  Thorax  in  der  Mittellinie  und 
des  Herzbeutels.  Der  linke  Ventrikel  inclusive  des  Septums  wird  mit  den 
Fingern  stark  comprimirt.  Carotisdruck  sinkt  auf  30.  Der  linke  Ventrikel 
pulsirt  einige  Secunden  mit  diesem  geriugen  Drucke  und  dann  erholt  er  sich 
allmahlich.  Nach  wiederholter  Quetschung  sinkt  der  Druck  wieder  auf  30 
und  allmahlich  noch  tiefer.  Im  Gegensatz  zu  dem  linken  Ventrikel  arbeitet 
der  rechte  3 — 4  Minuten  anscheinend  ungeschwacht  fort,  wahrend  welcher 
Zeit  sich  das  Blut  in  der  Lungenarterie.  den  beiden  Vorhofen,  dem  rechten 
Ventrikel  und  den  Korpervenen  deutlich  staut.  Der  Carotisdruck  sinkt  bis 
Null  und  nach  5  Minuten  wird  die  kiinstliche  Athmung  sistirt.  Das  Thier 
stirbt  ohne  Krampfe.  Die  Section  ergiebt  starkes  Lungenodem.  Es  finden 
sich  kleine  Blutungen  in  der  gequetschten  ^luskelwand  des  linken  Ventrikels 
und  kleine  Fibrinauflagerungen  auf  seiner  Innenflache. 

Versuch  10.  Kleines  Kaninehen.  Kiinstliche  Athmung.  Druck  in 
linker  Carotis  90 — 100  jVlm.  Hg.  Der  ganze  linke  Ventrikel  wird  zwischen 
zwei  auf  den  Branchen  einer  Pincette  befestigten  Korkplatte  comprimirt. 
Der  Carotisdruck  sinkt  ziemlich  rasch  bis  Null.  Der  rechte  Ventrikel 
pulsirt  1^ — 2  Minuten  fort  und  dann  stirbt  das  Thier  unter  Erstickungser- 
scheinungen.  Nachdem  der  rechte  Ventrikel  zu  pulsiren  aufgehort  hat, 
schlagen  wie  gewohnlich  die  Vorhofe  noch  weiter,  am  langsten  der  rechte. 
Die  Section  ergiebt  Oedem  beider  Lungen.  Die  Pulmonalarterie  und  rechte 
Herzhiilfte  sind  stark  ausgedehnt,  die  Korpervenen  gestaut. 

In  einigen  Fallen  wurde  der  linke  Ventrikel  durch  die  Quetschung 
voUkommen  zum  Stillstande  gebracht,  in  anderen  pulsirte  er  noch  mit 
schwachem  Drucke  fort,  in  alien  aber,  bei  welchen  Lungenodem  entstand, 
schlug  der  rechte  Ventrikel  noch  einige  Zeit  rhythmisch  und  anscheinend 
mit  ungeschwachter  Kraft  fort.  Natiirlich  aber  geniigt  der  Augenschein 
nicht  und  es  war  zur  Controlle  unbedingt  nothig,  den  rechten  Ventrikel 
gleichfalls  zu  lahmen  und  zwar  sowohl  ohne  Beeintrachtigung  des  linken 
wie  auch  mit  gleichzei tiger  Lahmung  desselben. 

Man  kann  den  rechten  Ventrikel  in  derselben  Weise  wie  den  linken  zur 
Lahmung  bringen,  nur  wird  dies  durch  die  Diinnwandigkeit  desselben 
erleichtert.  Ich  babe  eine  deutliche  Lahmung  des  rechten  Ventrikels  sowohl 
ohne  gleichzeitige  Beeintrachtigimg  des  linken,  wie  auch  mit  Quetschung  des 
letzteren,  mehrmals  erzeugt,  und  nie  Lungenodem  in  Folge 
davon   beobachtet.     Einen  Versuch  will  ich  als  Bcispiel  anfiihren. 

Versuch  11.  Mittelgrosses  Kaninehen.  Kiinstliche  Athmung. 
Quecksilberdnick  in  rochter  Carotis  lOO  :\Im.  Eroffnung  des  Thorax  in  der 
Mittellinie  und  dos  Poricards.  Rechter  Ventrikel  zwischen  den  Fingern 
zusammongepresst.  Der  Carotisdruck  sinkt  bis  30,  aber  nach  einer  Minute 
ist  er  wieder  auf  100 — 110  Mm.  gcstiegen.  Der  rechte  Ventrikel  wird  wieder 
gequet^cht,  Carotisdruck  20.    Der  rechte  Ventrikel  ist  deutlich  geliihmt  und 


ZUR  PATHOLOGIE  DES  LUNGENODEMS        31 

wird  mit  Blut  ausgedehut,  in  viel  starkerem  Grade  staut  sich  das  Blut  in  dem 
rechten  Vorliofe,  Der  linke  Ventrikel  pulsirt  fort  und  bietet  einen  auffallen- 
den  Contrast  zmn  rechten,  welcher  nach  kurzer  Zeit  bios  wurmformige  und 
dann  vibrirende  Bewegungen  macht,  Nach  ungefahr  2^  Minuten  stirbt  das 
Thier  mit  Krampfen.  Bei  der  Section  zeigen  sich  der  linke  Ventrikel  und  die 
Arterien  blutleer,  dagegen  die  Venen  strotzend  gef  iillt.  Es  ist  kein  Lungen- 
odem  vorhanden. 

In  Beriicksichtigung  der  Ergebnisse  dieser  Ver- 
suche  diirfen  wir  ohne  Bedenken  linksseitige  Herz- 
paralyse  als  eine  Causa  efficiens  von  Lungenodem 
betrachten.  Theoretische  Ueberlegungen  lassen  es  kaum  anders 
erwarten.  Wenn  der  rechte  Ventrikel  fortfahrt  Blut  in  die  Lungengefasse 
hineinzupumpen,  wahrend  der  linke  nur  einen  Bruchtheil  davon  forttreiben 
kann,  wenn  der  Unterschied  zwischen  den  Kraften  der  beiden  Ventrikel 
einen  gewissen  Grenzwerth  iiberschritten  hat,  dann  muss,  sclieint  mir,  der 
Druck  in  den  Lungencapillaren  so  hoeh  steigen,  dass  Lungenodem  die  Folge 
wird.  Der  Einwand,  dass  die  vemiinderte  Kraft  des  linken  Ventrikels  die 
Stromkraft  im  grossen  Kreislauf  so  herabsetzt,  dass  keine  fiir  diese  Druck- 
steigeruug  hinreichende  Blutmenge  in  den  rechten  Ventrikel  einfliesst,  ist 
am  besten  durch  das  Ergebniss  des  Versuches  beantwortet.  Dariiber  wie  die 
Stromgeschwindigkeit  sich  dabei  verhalt,  auch  iiber  die  absolute  Hohe  des 
fiir  das  Zustandekommen  von  Lungenodem  nothigen  Kraftunterschiedes  der 
beiden  Ventrikel  babe  ich  keine  experimentellen  Data,  und  theoretische 
Betrachtungen  iiber  diese  Punkte  batten  keinen  Worth. 

Diese  durch  das  Experiment  gestiitzte  Hypothese  bietet  meiner  Meinung 
nach  die  beste  Erklarung  der  Eigenthiimlichkeiten  des  Auftretens  von 
Lungenodem  beim  Menschen. 

Die  grossere  Schnelligkeit,  mit  welcher  Oedem  sich  in  der  Lunge  ent- 
wickelt  als  in  anderen  Korpertheilen,  findet  seine  Erklarung  in  der  absolut 
grosseren  Durchlassigkeit  der  Lungencapillaren,  oder,  besser  ausgedriickt, 
in  der  grosseren  Differenz  zwischen  dem  Seitendruck  in  den  Gef assen  und  den 
Widerstanden,  welche  der  durchdringenden  Fliissigkeit  entgegenstehen. 
Einerseits  bedingen  die  Ursachen  von  Lungenodem  einen  fiir  den  Pulmonal- 
kreislauf  verhaltnissmassig  hohen  Seitendruck,  andererseits  finden  die 
Lungencapillaren  nur  eine  schwache  Stiitze  an  dem  Lungengewebe.  Wenn 
man  bedenkt,  dass  unter  normalen  Verhaltnissen  die  Spannung  in  den 
Lungengefassen  sehr  gering  ist,  dass  sie  zu  einem  erstaunlichen  Grade  gegen 
Druckveranderujagen  im  grossen  Kreislauf  geschiitzt  sind,  dass  selbst  bedeu- 
tende  Storungen  im  Lungenkreislaui  mit  geringen  Druckiinderungen  aus- 
geglichen  werden  konnen,  so  begreift  man,  dass  sie  gegeniiber  den  physiolo- 
gischen  und  vielen  pathologischen  Verhaltnissen  einer  grosseren  Starke  nicht 
bediirfen.     We^en  der  ffiinstigen  Abdunstimo^sbedingungen  in  der  Lunge 


32  ZUR  PATHOLOGIE  DES  LUNGENODEMS 

uiid  wegen  des  durch  histologische  TJntersuchungen  wahrscheinlich  gemach- 
ten  reichlichen  Lymphabflusses  aus  derselben,  ware  es  iiberdies  leicht 
erklarlich,  dass  eine  bei  leichten  Dnicksteigeningen  moglicherweise  ein- 
tretende  vermehrte  Ausscheidung  aus  den  Lungencapillaren  ohne  storende 
Erscheinungen  ablaufen  konnte.  Wenn  aber  eine  plotzliche  und  hochgradige 
Drucksteigerung  in  den  Lungencapillaren  eintritt,  fiir  welche  die  obigen 
Yersuche  Beispiele  darbieten,  dann  verrathen  die  Capillaren  ihre  absolut 
geringere  Widerstandsfahigkeit  dadurch,  dass  Lungenodem  in  der  Zeit  von 
einer  oder  zwei  Minuten  und  noch  schneller  entstehen  kann.  Es  ist  eben 
dieses  stiirmische  Auftreten,  welches  eine  grosse  Anzahl  der  Falle  von  Oedema 
pulmonum  beim  Menschen  charakterisirt.  Seine  Erkliirung  liegt  auf  der 
Hand,  wenn  wir  die  Ursaehe  desselben  in  einer  plotzlichen  Schwachung  des 
linken  Ventrikels  suchen.  Mit  anderen  Erkliirungsweisen  scheint  es  mir 
dagegen  niclit  leicht  diesen  Charakter  des  Lungenodems  in  Einklang  zu 
bringen. 

Ein  weiteres  Merkmal  des  Lungenodems  ist  die  Inconstanz  seiner  Ent- 
btehung  bei  anscheinend  gleichen  Bedingungen.  Wenn  Lungenodem  bei  der 
Todesagonie  wegen  der  allgemeinen  Herzschwache  entstiinde,  wenn  die 
collaterale  Hyperamie  Oedem  der  einen  Lunge  bei  Hepatisation  der  anderen 
herbeifuhrte,  wenn  bei  einer  Mitralstenose  das  mechanische  Hindemiss  des 
Blutabflusses  oder  bei  Morbus  Brightii  die  Hydramie  die  Ursaehe  des  Oedems 
bildete,  warum  erscheint  es  dann  in  dem  einen  Falle  und  bleibt  in  dem 
anderen  aus,  obwohl  in  beiden  diese  Bedingungen  anscheinend  in  gleichem 
Grade  vorhanden  sind  ?  Diese  unter  den  obigen  Voraussetzimgen  so  rathsel- 
hafte  Inconstanz  ist  wohl  erklarlich,  wenn  wir  jene  Zustande  als  begiin- 
stigende  Momente  (Dispositio  ad  morbum)  betrachten,  aber  eine  vor- 
wiegende  Schwiiche  des  linken  Ventrikels  als  die 
nachste  Ursaehe  annehmen.  Wenn  bei  der  Agonie  zum  Beispiel  die  beiden 
Herzhalften  beim  Absterben  gleichen  Schritt  halten,  so  entsteht  kein  Lun- 
genodem, wenn  aber  der  linke  Ventrikel  vorauseilt  und  rascher  geliihmt  \vivd, 
als  der  rechte,  dann  kann  es  zu  Stande  kommen.  Dabei  wird  natiirlich  nicht 
gesagt,  dass  der  rechte  Ventrikel  nicht  gleichzeitig  audi  schwacher  werde; 
er  ist  sogar  wahrscheinlich  in  den  meisten  Fallen  von  Lungenodem  ge- 
schwacht.  Diese  Schwiiche  aber  begiinstigt  an  imd  fiir  sich  nicht  das  Auf- 
treten von  Lungenodem.  Gewiss  freilich  verliert  der  linke  Ventrikel  sein 
wunderbares  Anpassungsvemiogen  an  wechselnde  Widerstande,  veriinder- 
lichen  Fiillungsdruck  und  was  auch  sonst  fiir  regulatorische  Einrichtigungen 
der  Herzkraft  im  Spiel  sein  mogen,  nicht  eher  vollstandig,  als  bis  die  Leist- 
ungsfiihigkcit  des  g  a  n  z  e  n  Herzens  angegriffen  worden  ist.  So  entsteht  das 
Lungenodem,  welches  in  Verlauf  von  Herz-,  Lungen-,  Nierenkrankheiten 
u.  s.  w.  auftritt  erst  dann,  wenn  die  Gesammttbatigkeit  des  Herzens  herabge- 


ZUR  PATHOLOGIE  DES  LUNGEXODEMS        33 

setzt  ist,  und  deshalb  ist  man  zu  der  irrthumlichen  Meinung  gekommen,  dass 
aDgemeine  Herzschwache  allein  eine  Causa  efficiens  des  Hydrops  pulmo- 
num  sei. 

Hier  mochte  ich  einem  Einwand  begegnen,  welcher  sich  folgendennaassen 
ausdriicken  liesse.  Wenn  zuin  Beispiel  bei  einer  uncompensirten  Mitral- 
stenose  der  rechte  Ventrikel  den  vorhandenen  Widerstanden  nicht  gewach- 
sen  ist,  wie  kann  man  annehmen,  dass  bei  noch  gxosseren  Hindernissen  seine 
Kraft  ausreichen  werde,  um  die  fiir  die  Entstehung  von  Limgenodem  nothige 
Dnickhohe  zu  Stande  zu  bringen?  Aber  eben  diese  vermehrten  Wider- 
stiinde  sind  ein  Reiz  fiir  das  rechte  Herz;  wahrscheinlich  ist  der  Haupt- 
regulator  der  Herzkraft  in  den  vor  ihm  liegenden  Widerstanden  gelegen, 
und  obwohl  der  rechte  Ventrikel,  wahrscheinlich  selbst  in  normalem 
Zustande,  nicht  auf  die  Dauer  die  Druckhohe  behaupten  konnte,  welche  fiir 
die  Entstehung  von  Lungenodem  nothig  ist,  reagirt  er  doch,  selbst  in 
geschwachtem  Zustande,  fiir  eine  kurze  Zeit  auf  die  plotzlich  vermehrten 
Widerstande  mit  dem  nothigen  Kraftaufwand.  Das  rasche  Zuriicktreten  von 
Lungenodem  in  vielen  Fallen  ist  vielleicht  ebenso  sehr  auf  die  ungeniigende 
Kraft  des  rechten  Ventrikels  die  Stauung  langer  zu  behaupten,  wie  auf 
Herstellung  der  Kraft  des  linken  Herzens  zu  beziehen.  Dass  es  eine  minimale 
Grenze  giebt,  unter  welcher  die  Kraft  des  rechten  Ventrikels  nicht  mehr 
fahig  ist,  ein  Stauungsodem  zu  erzeugen,  betrachte  ich  als  sehr  wahrschein- 
lich, aber  es  sind  keine  Anhaltspunkte  vorhanden,  urn  zu  bestimmen,  wo 
diese  Grenze  liegt.  Und  vielleicht  ist  es  mehr  verminderte  Erregbarkeit,  als 
verminderte  Kraft  des  rechten  Ventrikels,  welche  der  Entstehung  von 
Lungenodem  hiuderlich  wird.  Da  aber  das  Oedem,  welches  ohne  vorherge- 
hende  bedeutende  allgemeine  Herzschwache  —  wie  gelegentlich  bei  Krank- 
heiten  der  Kreislaufsorgane,  sowie  bei  Gehimkrankheiten,  besonders  trau- 
matischer  Xatur  —  plotzlich  auftritt,  das  starkste  und  von  den  bedrohlich- 
sten  suffocatorischen  Erscheinuugen  begleitet  ist,  wahrend  dasjenige  der 
Todesagonie  oftmals  so  gering  ausfallt,  dass  man  zweifelt,  ob  es  iiberhaupt 
den  Namen  verdient,  so  konnen  wir  schliessen,  dass  es  fiir  den  Grad  des 
Limgenodems  nicht  gleichgiiltig  ist,  ob  eine  betrachtliche  allgemeine  Herz- 
schwache vorhergegangen  ist  oder  nicht. 

Wenn  ich  eine  linksseitige  Herzparalyse  als  die  Causa  proxima  des  acuten 
allgemeinen  Lungenodems  in  Anspruch  nehme,  so  meine  ich  nicht,  dass 
anderen  Momenten,  als  Herzfehlern,  Hydramie  etc.,  aller  Einfluss  abzu- 
sprechen  ist,  sondern  nur,  dass  diese  allein  uns  keine  befriedigende 
Erklarung  der  Entstehung  des  Oedema  pulmonum  geben. 

In  der  Entstehungsweise  und  in  den  Erscheinungen  von  Lungenodem 
beim  Menschen  ist  nichts,  was,  so  viel  ich  sehe,  gegen  die  auseinanderge- 
setzte  Hypothese  spricht,   wahrend  vieles   seine  vollkommene  Erklarung 


34  ZUR  PATHOLOGIE  DES  LUNGENODEMS 

dadurch  findet.  Ob  das  Vorhandensein  des  vorausgesetzten  Zustandes  des 
Herzens  am  Menschen  zu  beweisen  sei,  scheint  mir  zweifelhaft.  Das  von 
klinischer  Seite  "  hervorgehobene  Symptom  des  acuten  allgemeinen  Lungen- 
odems,  starker  Herzschlag  bei  schwachem  Pulse,  scheint  eine  Stiitze  fiir 
unsere  Auffassung  darzubieten,  doch  mochte  ich  nicht  zu  vieles  Gewicht 
darauf  legen,  da  auch  eine  Lungenstauung  aus  irgend  welcher  anderen 
Ursache  den  rechten  Ventrikel  secundar  zu  starkerer  Arbeit  veranlassen 
konnte.  Da  es  nur  in  untergeordnetem  Grade  auf  die  absolute  Kraft- 
leistimg  des  linken  oder  des  rechten  Ventrikels,  vielmehr  vorzugsweise  auf 
das  Verhiiltniss  zwischen  beiden  ankommt,  so  mag  es  schwierig  sein,  diese 
rehitive  Yerschiedenheit  klinisch  zu  constatiren,  indess  trotzdem  wird  sich 
vielleicht  die  Aufmerksamkeit  der  Elliniker  in  Zukunft  auf  diesen  Punkt 
rich  ten. 


Das  mikroskopischc  Bild  des  allgemeinen  Lungenodems  lasst  sich  mit 
wenigen  Worten  zusammenfassen.  Erzeugt  man  kiinstlich  Limgenodem, 
zum  Beispiel  durch  Unterbindung  der  aufsteigenden  Aorta,  und  nimmt,  ohne 
die  Lungen  beriihrt  zu  haben,  etwas  von  der  Oedemfliissigkeit  sorgfaltig  mit 
einer  Pipette  aus  der  Trachea  heraus,  so  finden  sich  darin  folgende  korper- 
liche  Elemente:  zahlreiche  rothe  Blutkorperchen,  Bronchialepithelien, 
sparsame  Lungenepithelien  und  freie  Kornchen  von  demselben  Aussehen, 
wie  diejenigen  in  den  Lungenepithelzellen,  selten  weisse  Blutkorperchen. 
Die  als  Lungenepithelien  angesprochenen  Zellen  sind  platt,  zwei-  bis  viermal 
so  gross  als  weisse  Blutkorperchen,  grob  granulirt,  rund  oder  oval,  enthalten 
jede  einen  bliischenformigen,  ovalen  Kern,  selten  deren  zwei,  und  kommen 
meistens  vereinzelt  vor.  Im  Verhaltnisse  zu  der  Menge  der  rothen  Blut- 
korperchen ist  jedenfalls  die  Anzahl  aller  iibrigen  Elemente  verschwindend 
klein. 

Schnitte  aus  der  menschlichen  odematosen  Lunge  zeigen  die  prachtvollste 
natiirliclie  Injection  der  Capillaren.  In  diesen  liegen  oft  die  Blutkorperchen 
zu  zweien  oder  dreien  in  einem  Querschnitt,  wahrend  gewohnlich,  selbst  in 
hyperamischen  Lungen,  bios  ein  einziges  Blutkorperchen  in  einem  Quer- 
schnitt Platz  findet.  Die  Capillaren  sind  mit  anderen  Worten  zwei-  bis  drei- 
fach  iiber  ihrc  normale  Weite  ausgedehnt.  Ausserhalb  der  Gefiisse  finden 
sich  viele  rothe  Blutkorperchen  in  den  Alveolen  und  den  Interstitien. 

Die  oben  als  Lungcnepithel  orvvahntcn  Zellen  findet  man  in  grosser  Menge 
an  Schnittcn  aus  der  f riscbcn  Lunge.  Aber,  wie  schon  Friedlander 
bervorgehoben  hat,  sind  sie  eden  so  zahlreich  und  mit  demselben  Aussehen 
an  Schnitten  jeder  frischen  Lunge  zu  sehen  und  bieten  deshalb  nichts  fiir 

"*  L  e  b  e  r  t ,  Handbuch  d.  pract.  Medicin. 


ZUR  PATHOLOGIE  DES  LUNGENODEMS  35 

Lungenodem  Charakteristisches.  Der  Befund  derselben  in  der  Tracheal- 
fliissigkeit  macht  es  wahrscheinlich,  dass  die  serose  Ausschwitzung  die 
Epithelien  in  derselben  Weise  ablest,  wie  dies  eine  indiffereute  Zusatzfliissig- 
keit  bei  der  mikroskopischen  Untersuchimg  thut.  Im  frischen  Zustand  ist 
fiir  diese  Zellen  das  am  meisten  Charakteristische  ihr  komiger  Inhalt.  Der- 
selbe  besteht  aus  Komchen  von  ziemlich  starkem  Glanz,  welehe  oftmals 
dicht  um  den  Kern  gehauft  liegen,  Zwischen  dem  komigen  Inhalt  und  der 
einfachen  Zellcontour  befindet  sich  ein  blasser  Hof,  welcher  sich  nach  Wasser- 
zusatz  aufblaht.  Die  Kornchen  sind  theils  eiweissartiger,  theils  fettiger 
Natur.  Nach  Zusatz  von  Essigsaure  werden  die  Zellen  blasser,  aber  ein 
bedeutender  Theil  der  Kornchen  bleiben  noch.  An  Schnitten  von  in  Alkohol 
geharteten  Praparaten  sind  die  Epithelzellen  schwer  als  solche  zu  erkennen, 
weil  ihr  korniger  Inhalt  meistens  verschwunden  ist,  und  die  Kerne  nicht 
leicht  von  den  Capillarkemen  zu  unterscheiden  sind. 


THEORY  OF  PULMONARY  OEDEMA' 

I  am  glad  to  comply  with  your  kind  invitation  to  say  something  concern- 
ing the  theory  of  the  causation  of  certain  forms  of  pulmonary  oedema  which 
I  advanced  25  years  ago  on  the  basis  of  an  experimental  research  under- 
taken at  the  suggestion  and  under  the  supervision  of  my  honored  teacher, 
Professor  Cohnheim,  in  his  laboratory  in  Breslau.  This  research  was  the 
first  experimental  study  of  the  subject,  and  Professor  Sahli,  one  of  the  lead- 
ing critics  of  the  theory,  has  been  good  enough  to  say  that  "  even  the  oppo- 
nents of  the  theory  need  not  hesitate  to  give  it  praise  of  having  for  the 
first  time  directed,  upon  the  firm  foundation  of  pathological  experiment, 
the  pathology  of  pulmonary  oedema  into  straight  and  serviceable  paths." 

Permit  me  to  recall  some  of  the  leading  results  and  conclusions  of  my 
investigation,  published  in  "  Virchow's  Archiv,"  in  March,  1878.  These 
related  to  acute  general  oedema  of  the  lungs,  from  wliich  the  inflammatory 
forms  of  oedema  were  separated.  The  various  hypotheses  current  at  that 
time,  concerning  the  causation  of  pulmonary  oedema,  were  subjected  to  a 
critical  analysis,  based  in  part  upon  experimental  work,  and  all  wore  rejected 

*  The  following  is  an  introductory  note  by  S.  J.  Meltzer  which  states  the 
reason  for  including  a  letter  from  Dr.  Welch  in  Meltzer's  publication  on 
Oedema  in  1904:  "Welch's  Theory  of  Pulmonary  Edema. — In  discussing  the 
various  forms  of  edema  in  the  first  edition  of  his  brilliant  lectures  on  general 
pathology,  Cohnheim  remarked  that  there  is  one  form  of  edema,  a  most 
important  one,  for  which  he  could  as  yet  offer  no  adequate  explanation;  this 
is  pulmonary  edema.  But  soon  after,  pulmonary  edema  was  elucidated  by  a 
theory  which  still  occupies  a  commanding  position  in  general  pathology.  The 
theory  was  based  upon  an  extensive  series  of  experiments  carried  out  in 
the  laboratory  of  Cohnheim  by  an  investigator  who  is  now  our  foremost 
pathologist  in  this  country — I  refer  to  Dr.  William  H.  Welch,  of  Johns  Hop- 
kins University.  It  is  Just  twenty-five  years  since  the  theory  was  advanced. 
In  the  course  of  this  quarter  of  a  century  the  theory  was  tested  experimentally, 
discussed  and  criticized  by  Sahli,  Grossmann,  and  Lowit.  It  seemed  to  me 
that  it  would  be  highly  instructive  to  hear  the  originator  of  this  theory  present 
and  discuss  it  again  in  his  concise  way.  Professor  Welch  complied  with  my 
request,  for  which  I  wish  here  to  express  my  gratitude.  Permit  me  to  read 
to  you  the  remarks  written  down  by  Prof.  Welch  on  his  theory  of  pulmonary 
edema." 

In:  Edema,  a  Consideration  of  the  Physiologic  and  Pathologic  Factors  Con- 
cerned in  its  Formation,  by  S.  .1.  Meltzer,  New  York. 

Am.    Med.,    Phlla.,    1904,    VIII,    195-196. 

36 


THEORY  OF  PULMONAEY  OEDEMA         37 

as  unsupported  or  directly  opposed  by  established  facts.  Although  some 
of  these  hypothetic  causes  of  pulmonary  oedema,  such  as  active  hyperaemia, 
enfeebled  action  of  the  entire  heart,  and  passive  hyperaemia  due  to  mitral 
and  aortic  valvular  disease,  continue  to  be  prominently  mentioned  in  some 
textbooks,  I  consider  that  the  criticism  passed  upon  them  is  still  valid,  and 
that  no  satisfactory  additional  evidence  in  their  support  has  been  furnished. 

My  investigations  were  directed  mainly  toward  a  solution  of  the  question 
whether  acute  general  pulmonar}'  oedema  belongs  to  the  group  of  the  so-called 
mechanical  oedemas,  referable  to  passive  hyperaemia,  or  to  that  other  group, 
of  more  obscure  causation,  which  includes  the  hydraemic  or  cachectic  oedemas, 
and  which  was  at  that  time,  and  is  still,  often  attributed  to  changes  in  the 
vascular  walls.  Even  25  years  ago  it  was  recognized  by  Cohnheim  that 
other  than  mechanical  factors  are  concerned  in  the  oedemas  due  to  venous 
congestion,  and  especially  that  these  are  not  the  direct  result  of  rise  of 
of  intracapillary  pressure,  but  for  the  purposes  of  my  research  it  was  not 
deemed  necessary  to  consider  how  passive  hyperaemia  induced  oedema.  The 
essential  thing  was  to  determine  whether  or  not  acute  general  oedema  of  the 
lungs  belongs  to  this  latter  categor}-. 

Acute  general  oedema  of  the  lungs  is  characterized  by  several  features, 
which  seem  to  give  it  a  position  quite  apart  from  oedemas  of  other  parts  of 
the  body.  Among  these  distinctive  features  may  be  mentioned  the  often 
rapid  or  sudden  onset  of  the  affection,  sometimes  its  quick  disappearance, 
its  occurrence  as  an  occasional  complication  of  a  great  variety  of  acute 
and  of  chronic  diseases,  although  a  constant  accompaniment  of  none,  and 
its  frequency  as  a  terminal  or  even  agonal  event.  Whatever  be  the  explana- 
tion adopted,  it  must  take  cognizance  of  these  and  other  peculiar  characters 
of  pulmonary  oedema.  In  view  of  these  characters,  and  of  previous  work 
by  himself  and  Lichtheim,  relating  to  the  pulmonary  circulation.  Professor 
Cohnheim,  when  I  began  my  experiments,  considered  it  improbable  that 
oedema  of  the  lungs  would  be  shown  to  be  a  "  Stauungscedem  "  or  conges- 
tive oedema. 

I  endeavored  in  the  first  place  to  determine  whether  it  is  possible  to  pro- 
duce, experimentally,  oedema  of  the  lungs  by  obstruction  to  the  outflow  of 
blood  from  the  pulmonary  veins.  The  previous  experiments  of  Cohnheim 
and  Lichtheim  had  already  demonstrated  that  very  great  increase  of  the 
blood-pressure  in  the  aorta  may  occur  with  relatively  little  effect  upon  the 
pressure  in  the  pulmonary  vessels,  and  also  that  the  right  ventricle  is  capable 
of  overcoming  enormous  obstacles  in  the  pulmonar}'  circulation  without 
material  lowering  of  the  aortic  pressure.  My  experiments  confirmed  and 
extended  these  results.  I  succeeded,  however,  in  producing  oedema  of  the 
lungs,  both  by  ligation  of  the  aorta  and  its  branches,  and  by  ligation  of  pul- 


38         THEORY  OF  PULMONARY  OEDEMA 

nionary  veins;  but  the  degree  of  obstruction  to  the  circulation  in  the  aorta 
or  in  the  pulmonary  veins  necessary  to  bring  about  this  result,  was  found 
to  be  t^o  enormous  that  it  is  scarcely  conceivable  that  it  could,  under  any 
circumstances,  occur  in  human  beings. 

The  experiments  thus  far,  while  proving  the  possibility  of  the  occurrence 
of  pulmonary  oedema  in  consequence  of  passive  hyperaemia,  not  only  shed  no 
light  upon  the  conditions  actually  concerned  in  the  production  of  this 
affection  in  Imman  beings,  but,  on  the  other  hand,  tended  to  discredit  the 
causative  factors  which  had  previously  been  based  upon  this  assumption. 

The  possible  ways  in  which  venous  hyperaemia  of  the  lungs  might  be 
induced  were  not,  however,  exhausted  by  experiments  mentioned.  There 
occurred  to  me  as  a  possible  mechanical  explanation  of  pulmonary  oedema, 
a  condition  which  I  described  in  the  following  words:  "A  disproportion 
between  the  working  power  of  the  left  ventricle  and  of  the  right  ventricle 
of  such  character  that,  the  resistance  remaining  the  same,  the  left  heart  is 
unable  to  expel  in  a  unit  of  time  the  same  quantity  of  blood  as  the  right 
heart."  I  lay  some  stress  upon  this  mode  of  statement  of  my  theory,  and 
emphasized  it  by  the  type  in  my  article.  It  is  true  that  I  mentioned  and 
examined  experimentally  only  paralysis  of  the  left  ventricle  as  a  cause  of 
this  incongruity  between  the  two  sides  of  the  heart,  but  it  is  evident,  as  was 
mentioned  by  Cohnheim  soon  afterward,  that  spasm  of  the  left  ventricle 
might  bring  about  the  same  result. 

The  experimental  test  of  this  hypothesis  is  a  matter  of  great  difficulty. 
I  sought  in  vain  for  some  poison  which  would  act  in  the  desired  way  upon 
the  left  ventricle.  Although  several  poisons  occasionally  produced  oedema 
of  the  lungs,  none  did  so  constantly,  and  I  was  unable  to  demonstrate  in 
this  way  an  isolated,  paralyzing  effect  on  the  left  ventricle.  I  succeeded, 
however,  in  paralyzing  the  left  ventricle  of  rabbits  by  the  coarse  procedure 
of  squeezing  it  between  the  fingers,  and  I  observed  in  many  instances  after 
this  manipulation,  continued,  apparently  forcible  action  of  the  right  ven- 
tricle with  diminished  force  of  the  left  ventricle,  as  indicated  by  the  pres- 
sure in  tiie  carotid  artery.  Under  these  circumstances  well-marked  pul- 
monar\-  oedema  resulted.  It  is  this  experiment  upon  the  rabbit  which  con- 
stituted the  experimental  basis  of  the  theory  of  pulmonary  oedema  advanced 
in  my  article  on  the  subject. 

I  considered  briefly  the  nature  of  the  forces  which  might  be  operative  in 
supplying  the  right  ventricle  with  the  requisite  amount  of  blood  for  the 
production  of  pulmonary  oedema  after  lessened  output  from  the  left  ven- 
tricle, and  to  this  aspec-t  of  the  subject  Sigmund  Mayer,  shortly  after  my 
publication,  devoted  especial  attention. 


THEORY  OF  PULMONAEY  OEDEMA         39 

I  was  not  unmindful  of  the  fact  that  this  theory,  if  applicable  to  human 
beings,  must  conform  to  clinical  and  anatomical  observations,  and  I  endeav- 
ored to  point  out  that  it  not  only  was  not  contradicted  by  such  observations, 
but  that  it  furnished  a  better  explanation  than  any  other  hypothesis,  known 
at  that  time,  of  many  cases  of  acute  general  pulmonary  oedema  in  man. 

Of  the  fate  of  this  theory  during  the  quarter  of  a  century  since  its  pub- 
lication it  is  impossible  for  me  to  speak  in  detail  in  this  necessarily  brief 
communication,  but  there  are  a  few  points  upon  which  I  should  like  to 
touch.  The  theory  has  obtained  wide,  although  by  no  means  universal 
acceptance,  in  German  and  Russian  publications,  being  unreservedly  adopted, 
for  example,  by  such  eminent  clinicians  as  Striimpell  and  Eichhorst.  It 
seems  to  be  little  known  and  has  been  but  little  discussed  by  American,  En- 
glish and  French  writers.  The  experimental  results  have  been  abundantly 
confirmed  and  extended,  although  not  all  are  agreed  in  their  interpretation. 

Grossmann,  in  an  interesting  experimental  study  of  pulmonary  oedema  due 
to  poisoning  by  muscarin,  believes  that  he  has  demonstrated  that  this  form 
of  oedema  is  due  to  spasm  of  the  left  ventricle  with  resulting  venous  hyper- 
aemia  of  the  lungs,  and  that  the  same  condition  of  the  left  ventricle  is  present 
in  many  cases  of  human  pulmonary  oedema.  This  opinion  is  not,  as  Gross- 
mann seems  to  suppose,  opposed  to  the  fundamental  conception  underlying 
my  theory — namely,  a  disproportion  between  the  action  of  the  two  ventricles 
in  the  sense  that  the  left  ventricle  propels  in  a  unit  of  time  only  a  fraction  of 
the  quantity  of  blood  expelled  by  the  right  ventricle  into  the  pulmonary 
artery.  It  seems  to  me,  however,  more  probable  that  an  enfeebled  action  of 
the  left  ventricle,  rather  than  a  spasmodic  action,  is  likely  to  be  the  cause  of 
this  disproportion  under  the  conditions  in  which  pulmonary  oedema  ordi- 
narily occurs. 

The  most  important  criticism  to  wliich  my  theory  of  pulmonary  oedema  has 
been  subjected,  is  by  Sahli,  in  a  valuable  paper  published  in  1885.  The 
strongest  points  in  his  argument  against  the  theory  are  that  the  radial  pulse 
in  eases  of  pulmonary  oedema  to  which  my  explanation  might  be  applied, 
does  not  indicate  paralysis  of  the  left  ventricle,  and  that  the  anatomical  con- 
dition is  not  one  of  hyperaemia.  Both  of  these  possible  objections  had 
occurred  to  me,  and  Sahli  is  in  error  in  stating  that  my  theory  was  promul- 
gated without  consideration  on  my  part  whether  the  pathological-anatomical 
condition  of  human  oedematous  lungs  is  one  of  hyperaemia. 

I  stated  in  my  article  that  it  seemed  to  me  doubtful  whether  clinical 
methods  could  determine  whether  the  assumed  relative  disproportion  between 
the  work  of  the  two  ventricles  existed  or  not.  In  my  judgment,  Sahli  is 
mistaken  in  supposing  that  the  paralysis  of  the  left  ventricle  must  be  almost 
complete  in  order  that  the  degree  of  passive  hyperaemia  requisite  for  the 


40         THEORY  OF  PULMONARY  OEDEMA 

production  of  pulmonary  oedema  should  ensue.  As  is  well  known,  it  is 
absolutely  essential  for  the  integrity  of  the  circulation  and  the  continuance 
of  life,  that  each  ventricle  should  pump  into  its  artery  the  same  quantity 
of  blood  in  a  given  time.  This  is  the  central  fact  of  the  circulation,  and  is 
secured  under  normal  conditions  by  regulatory  mechanisms  of  the  most 
perfect  order.  The  disturbance  implied  by  interference  with  this  mechanism 
is  profound,  and  hence,  in  accordance  with  my  theory,  pulmonarj'  oedema 
is  practically  unknown  in  previously  healthy  persons.  Let,  however,  this 
mechanism  be  so  disturbed  that  at  each  systole,  the  right  ventricle  throws 
even  a  little  more  blood  into  the  pulmonary  artery  than  does  the  left  ventricle 
into  the  aorta ;  then  it  will  not  be  long  before  there  is  a  large  excess  of  blood 
in  the  pulmonary  vessels.  What  is  in  the  first  instance  essential  is  not  the 
absolute  force  of  either  the  right  or  of  the  left  ventricle,  but  rather  the 
relation  between  these.  Hence  I  do  not  consider  that  the  condition  of  the 
peripheral  pulse  affords  satisfactory  indication  whether  the  heart  is  dis- 
turbed in  the  sense  required  by  my  theory. 

The  difficulty  or  impracticability  of  upsetting,  in  the  case  of  healthy 
animals,  the  remarkable  mechanism  which  coordinates  the  relative  force 
of  the  two  ventricles  by  an  experimental  procedure  which  stops  sliort  of  a 
high  degree  of  paralysis  of  the  left  ventricle,  is  doubtless  what  might  be 
expected  under  these  conditions,  but  it  is  reasonable  to  suppose  that  in  those 
severe  affections  of  human  beings  which  are  associated  with  general  pul- 
monar}'  oedema,  this  coordinating  mechanism  may  be  disturbed  far  more 
readily  and  without  extreme  grade  of  paralysis  of  the  left  ventricle.  The 
experiment  upon  the  rabbit,  already  cited  in  support  of  the  theory,  must 
be  considered  as  only  a  crude  and  imperfect  reproduction  of  the  condition 
assumed  to  underlie  the  onset  of  pulmonary  oedema  in  man. 

Sahli  contends  that  the  pallor  of  many  oedematous  lungs  proves  that  the 
oedema  is  not  of  a  congestive  type.  He  seems  to  have  made  no  microscopical 
examination  of  such  lungs.  I  describe  in  my  article  the  microscopical  char- 
acters of  general  pulmonary  oedema  in  human  beings,  and  there,  it  seems 
to  me,  show  conclusively  that  the  oedema  is  one  usually  associated  with  venous 
hyperaemia.  Certainly  the  enonnous  distention  of  the  capillaries,  the  large 
number  of  corpuscles  in  the  serous  transudate  and  the  richness  in  albumin 
of  this  transudate,  are  features  of  congestive  rather  tlian  of  hydraemic  or 
cachectic  oedema.  The  color  of  dropsical  tissues  is  an  unsafe  guide  for 
judging  their  blood-contents,  and.  while  in  my  experience,  lungs  which  are 
the  seat  of  general  oedema,  often  onou^-h  show  to  the  naked  eye  the  evidences 
of  hyperaemia,  I  have  often  been  surprised  to  find,  even  in  the  paler  lungs, 
by  microscopical  examination,  marked  hyperaemia  and  diapedesis  of  red 
corpuscles.    Renant  and  others  have  made  similar  observations. 


THEOEY  OF  PULMONARY  OEDEMA         41 

Lowit,  in  an  experimental  research  published  in  1893,  reached  the  con- 
clusion that  congestive  oedema  of  the  lungs  is  the  result  of  obstructed  outflow 
of  blood  from  the  pulmonary  veins  associated  with  increased  inflow  of  blood 
into  the  pulmonary  artery.  It  is  only  through  a  misconception  of  my  theory 
of  disproportionate  action  of  the  two  ventricles,  that  Lowit  should  find  any 
conflict  between  his  conclusion  and  the  essence  of  this  theory.  Lowit's  main 
contention,  however,  that  rise  of  pressure  in  the  pulmonar}'  artery  attends 
obstructed  outflow  from  the  pulmonarj'  veins  only  when  the  supply  of  blood 
to  the  pulmonary  artery  is  increased,  is  opposed  by  the  results  not  only  of 
his  predecessors,  but  also  of  Grossmann  and  other  experimenters.  I  agree 
also  with  Grossmann,  in  opposition  to  Lowit,  that  increased  supply  of  blood 
to  the  pulmonary  artery  is  not  essential  for  the  production  of  congestive 
oedema  of  the  lungs,  although  it  is  a  self-evident  corollary  of  my  theory,  as 
was  pointed  out  in  my  article,  that  given  the  requisite  disproportion  between 
the  action  of  the  two  ventricles,  the  higher  the  pressure  in  the  pulmonary 
artery,  the  more  favorable  are  the  conditions  for  the  production  of  pul- 
monary oedema. 

Incomprehensible  to  me,  as  indeed  it  has  been  to  others,  and  entirely  with- 
out experimental  support,  is  the  opinion  expressed  in  a  criticism  of  my  theory 
by  Jiirgensen,  that  paralysis  of  the  right  ventricle  leads  to  pulmonary 
hyperaemia  and  oedema  of  the  lungs. 

It  is  hardly  necessarj'  to  state  that  such  factors  as  changes  in  osmotic  pres- 
sure, alterations  in  the  capillary  endothelium,  interference  with  the  absorp- 
tion of  lymph,  which  have  become  prominent  in  the  later  discussions  of  the 
causation  of  oedema  may  be  utilized  in  the  explanations  of  pulmonary 
oedema,  as  of  congestive  oedema  elsewhere,  but  I  flnd  great  difficulty  in  con- 
ceiving any  of  these  factors  alone  to  be  the  primary  cause  of  acute  general 
oedema  of  the  lungs. 

In  one  respect  I  am  in  agreement  with  Sahli;  namely,  that  a  larger 
number  of  cases  of  pulmonary  oedema  are  referable  to  inflammatory  changes 
in  the  vascular  walls  than  is  generally  supposed.  My  opinion  is  based  upon 
the  results  of  the  systematic  bacteriological  examinations  which  are  made  at 
all  autopsies  at  the  Johns  Hopkins  Hospital.  Not  only  in  irregular  and 
localized  oedemas,  but  also  in  not  a  few  extensive  and  even  general  pulmonary 
oedemas,  plate  cultures  from  the  lungs  show  numerous  colonies  of  bacteria, 
most  frequently  streptococci  and  lanceolate  micrococci,  so  numerous  that 
they  must  have  been  in  active  growth  in  the  lungs. 


THE  BEHAVIOUR  OF  THE  RED  BLOOD-CORPUSCLES  WHEN 
SHAKEN  WITH  INDIFFERENT   SUBSTANCES' 

While  the  action  of  chemical  reagents  upon  the  red  blood-corpuscles  has 
been  often  studied,  comparatively  little  attention  has  been  given  to  the 
changes  produced  in  the  corpuscles  by  agents  which  act  mechanically.  As 
regards  the  effect  of  forcible  compression  of  the  red  blood-corpuscles, 
Vintschgau  observed  that  by  pressing  the  cover-glass  upon  a  drop  of  blood, 
sharp-bordered  fragments  of  the  red  blood-corpuscles  are  produced.  Another 
possible  mode  of  acting  mechanically  upon  the  red  blood-corpuscles  and  the 
one  which  we  have  adopted  is  to  shake  the  blood  with  finely  and  coarsely 
granular  insoluble  substances.  Although  we  at  first  undertook  these  experi- 
ments with  reference  to  their  bearing  upon  another  theme,  it  was  found  that 
the  results  of  these  provisional  experiments  were  not  so  simple  or  so  easily 
obtained  as  had  been  anticipated,  so  that  they  seem  to  merit  a  separate 
communication. 

Rollett '  has  already  adopted  the  procedure  of  shaking  the  blood  with 
insoluble  substances,  but  from  a  chemical  not  from  a  mechanical  point  of 
view.  He  observed  that  by  shaking  the  blood  with  certain  insoluble  sub- 
stances oxyhaemoglobin  is  reduced  to  haemoglobin.  Rollett  supposed  that 
after  long-continued  shaking  some  blood-corpuscles  must  be  destroyed  inas- 
much as  the  red  colour  of  the  blood  cannot  be  restored  by  shaking  with  air. 

We  at  first  adopted  the  simple  method  of  shaking  the  blood  in  a  test  tube 
with  iron-filings  for  ten  to  fifteen  minutes.  Although  this  seemed  to  cause 
a  diminution  in  the  number  of  red  blood-corpuscles  the  results  were  not 
sufficiently  clear  and  unmistakable,  especially  when  undiluted  blood  was 
used.  It  is  not  necessary  to  mention  here  all  of  the  other  methods  which 
were  attempted,  for  all  dilHiailties  were  overcome  as  soon  as  it  became 
possible  to  shake  the  blood  as  long  as  it  was  wished.  Through  the  kindness 
of  ^Ir.  Carl  H.  Schultz  there  was  placed  at  our  disposal  in  his  manufactory 
of  mineral  waters  a  machine  for  sliaking  bottles.  This  machine,  which 
could  be  kept  in  motion  the  whole  day,  possessed  an  apparatus  on  which 
several  bottles  could  be  fjistened  parallel  to  each  other  and  shaken  to  and  fro 
longitudinally.  There  were  180  excursions  a  minute,  tlie  length  of  each 
excursion  was  31)  cm.,  the  velocity  was  therefore  LIT  M.  per  second.     We 

'  S.  J.  Meltzer  and    W.   H.  Welch. 

J.   Phy.-^iol.,   I^nd.,    1884-85,  V,   255-260. 
'Hollett:    Sitzgber.  (1.  Wiener  Akad.  Math.-naturwis.    CI.    LII,  Abth.  2. 
42 


BEHAVIOUR  OF  EED  BLOOD-CORPUSCLES  43 

were  thus  enabled  to  shake  the  blood  not  only  hours  but  days  and  weeks  at  a 
time.  By  shaking  different  bottles  at  the  same  time  and  under  the  same 
conditions  it  was  possible  to  study  the  action  of  different  substances  as  well 
as  the  action  of  the  same  substance  according  to  the  coarseness  of  its  particles. 

When  it  was  not  our  object  to  observe  the  effect  of  varying  the  ratio 
between  the  quantity  of  the  substance  and  that  of  the  blood,  we  took  15  c.c. 
each  of  the  substance  and  of  the  blood,  either  undiluted  or  diluted  with 
physiological  salt  solution  (0.6;^).  Bottles  holding  100  c.c.  were  always 
employed,  so  that  there  was  a  column  of  air  over  the  fluid  to  be  shaken  (in 
contrast  with  Rollett's  experiments  with  exclusion  of  air).  The  fresh 
defibrinated  blood  of  the  ox  was  used.  This  is  especially  mentioned  because 
according  to  Rollett  the  blood  of  different  species  of  animals  is  reduced  with 
varying  degrees  of  rapidity. 

In  general  it  may  be  said  that  after  shaking  the  blood  for  a  considerable 
time  with  granular  insoluble  substances  a  period  is  reached  when  the  blood 
attains  the  maximum  degree  of  darkness  in  colour  and  all  the  red  blood- 
corpuscles  have  disappeared. 

Furthermore,  the  blood-corpuscles  disappear  the  sooner;  (a)  the  greater 
the  specific  gravity  of  the  substance  used,  (&)  the  finer  the  particles  of  the 
substance,  (c)  the  larger  the  quantity  of  the  substance  in  proportion  to  that 
of  the  blood,  and  (d)  the  smaller  the  number  of  blood-corpuscles  contained 
in  the  fluid,  that  is  more  rapidly  in  diluted  blood  than  in  undiluted  blood. 

The  blood  was  shaken  with  fragments  of  pumice-stone,  sand,  iron,  lead, 
copper,  brass  and  quicksilver.  Iron  and  brass  were  employed  in  varying 
degrees  of  fineness  of  the  particles.'  We  also  used  with  success  lead-shot 
about  2  mm.  in  diameter.  The  longest  time  necessary  for  the  disappearance 
of  the  red  blood-corpuscles — nearly  three  days — was  required  by  lead-shot 
on  account  of  the  coarseness  of  the  particles,  and  by  pumice-stone  on 
account  of  the  low  specific  gravity.  The  shortest  time — 7  to  8  hours — was 
required  by  quicksilver  on  account  of  its  weight  and  the  fineness  of  the 
particles  into  which  it  can  be  divided.  Rollett  *  asserts  that  the  reduction 
of  oxyhaemoglobin  takes  place  with  silver  much  more  slowly  than  with  iron, 
and  that  quicksilver  and  platinum  are  without  reducing  power.     For  our 

'Rollett  in  Hermann's  Handb.  d.  Phys.  Bd.  IV,  1,  p.  55,  says:  "Oxyhaemo- 
globin yields  its  loosely  combined  oxygen  to  reducing  substances iron 

filings  (Rollett),  still  better  Ferrum  hydrarg.  reduct.  (Ludwig  and  A.  Schmidt) 
and  is  changed  to  reduced  haemoglobin."  The  original  article  of  Ludwig  and 
Schmidt  was  not  accessible  to  us.  It  is  possible  that  the  greater  efficacy  of 
ferrum  reductum  is  due  to  the  greater  fineness  of  its  particles.  We  found  also 
in  our  experiments  that  reduced  iron  is  more  effective  than  iron  filings.  This 
was  not,  however,  the  case  when  the  finest  powder  obtained  by  straining  the 
substance  was   used. 

'  Rollett,  loc.  cit. 


44  BEHAVIOUR  OF  RED  BLOOD-CORPUSCLES 

puq^ose,  however,  we  have  found  quicksilver  the  most  effective  of  all  agents, 
so  that  in  our  further  experiments  we  have  used  it  exclusively. 

In  order  to  study  the  transitional  stages  before  the  complete  disappear- 
ance of  the  red  blood-corpuscles  we  have  shaken  for  different  periods  of 
time — one  hour,  two  hours,  three  hours,  etc. — several  bottles  each  containing 
15  c.c.  of  blood  and  15  c.c.  of  mercury.  With  the  naked  eye  one  can  clearly 
follow  the  gradual  change  in  colour.  At  the  end  of  an  hour  the  blood  appears 
much  darker  in  colour  than  the  unshaken  specimen.  From  hour  to  hour 
the  shaken  blood  becomes  darker  and  darker  in  colour,  until  at  the  end  of 
about  7  hours  it  becomes  absolutely  black,  and  from  that  time  on  no  further 
change  can  be  observed.  Microscopically  no  distinct  change  can  be  seen 
until  the  third  hour.  From  that  time  on  the  red  blood-corpuscles  disappear 
more  and  more,  those  which  remain  seem  to  become  somewhat  paler  while 
the  intervening  fluid  becomes  less  clear  and  transparent.  The  diminution 
in  number  of  the  red  blood-corpuscles  continues  for  several  hours,  not,  how- 
ever with  uniformity.  The  largest  number  of  corpuscles  disappear  somewhat 
suddenly  between  tlie  5th  and  6th  hour.  Up  to  this  time  the  diminution  is 
relatively  small.  The  few  corpuscles  which  remain  after  the  main  loss 
often  resist  destruction  for  a  long  time. 

There  can  be  no  doubt  that  the  cause  of  the  disappearance  of  the  red 
blood-corpuscles  is  a  mechanical  one.  The  reduction  of  haemoglobin  which 
follows  shaking  the  blood  for  a  short  time  was  interpreted  by  Rollett  as  a 
mechanical  effect,  although  this  view  rested  on  a  less  firm  basis  than  in  our 
experiments,  for  he  failed  to  obtain  this  reduction  by  the  heaviest  metals. 
In  our  experiments  we  have  found  that  the  result  depended  not  upon  the 
chemical  constitution  of  the  substances  employed  but  upon  their  quantity, 
their  specific  gravity,  and  the  fineness  of  their  particles,  all  purely  mechanical 
conditions. 

In  what  way,  however,  the  blood-corpuscles  disappear  and  just  what  be- 
comes of  them  we  could  not  positively  determine.  It  was  to  be  expected 
that  the  blood-corpuscles  by  being  shaken  with  finely  di\ided  indifferent 
substances  either  would  i)e  broken  into  fragments,  as  by  pressure  upon  the 
cover-glass,  or  would  lose  their  haemoglobin  and  be  converted  into  stromata 
or  shadows.  We  have  diligently  sought  both  for  fragments  and  for  shadows 
of  the  blood-corpuscles,  but  we  have  not  been  able  to  discover  either,  although 
in  the  course  of  our  experiments,  reagents  were  found  capable  of  demonstrate 
ing  the  most  invisible  shadows.  The  destruction  of  the  red  blood-corpuscles 
under  these  circumstances  appears  therefore  to  be  molecular  and  tolerably 
sudden.  A  certain  commotion  of  the  haemoglobin  in  the  blood-corpuscles 
appears  to  precede  their  complete  destruction.  It  has  already  been  men- 
tioned that  before  their  disappearance  the  red  blood-corpuscles  lose  some  of 
their  colouring  matter.    To  this  fact  is  to  be  added  the  following  noteworthy 


SHAKEN  WITH  INDIFFERENT  SUBSTANCES  45 

observation.  If  the  blood  be  shaken  with  any  of  the  substances  mentioned 
for  a  period  so  short  that  no  visible  change  in  the  blood  has  occurred,  and 
then  the  blood  be  allowed  to  stand  at  rest,  it  will  be  found  that  at  the  end 
of  15  to  18  hours  nearly  all  the  red  blood-corpuscles  have  completely  lost 
their  colouring  matter,  while  the  corpuscles  in  the  control-specimen  are  still 
wholly  intact.  A  shaking  therefore  of  only  short  duration  suffices  to  render 
less  firm  the  combination  between  stroma  and  haemoglobin.  It  is  perhaps 
only  this  loosening  of  the  combination  between  haemoglobin  and  stroma  and 
not  the  expulsion  of  the  haemoglobin  which  is  accomplished  by  the  shaking. 
Tlie  complete  separation  of  the  haemoglobin  from  the  corpuscle  and  its 
solution  in  the  surrounding  fluid  occurs  afterward.  Continued  shaking 
hastens  but  little,  it  may  be,  the  separation  of  the  haemoglobin  from  the 
blood-corpuscles;  it  causes  apparently  a  molecular  destruction  of  the  blood- 
corpuscles  before  the  haemoglobin  has  left  them. 

It  may  also  be  noted  that  all  blood-corpuscles  do  not  possess  equal  power 
of  resistance  (cohesion?).  Mention  has  already  been  made  of  Rollett's 
observation  that  the  reduction  of  haemoglobin  takes  place  with  varying 
rapidity  in  the  blood  of  different  species  of  animals.  In  our  experiments  it 
was  found  that  tlie  greater  number  of  red  blood-corpuscles  disappeared  at 
about  the  same  time,  while  a  small  fraction  disappeared  either  earlier  or 
later.  May  not  this  be  interpreted  as  in  favour  of  a  greater  or  less  cohesive 
power  in  certain  corpuscles  in  contrast  with  the  average  cohesive  power  of 
the  majority  of  corpuscles?  A  similar  supposition  is  made  with  reference 
to  those  corpuscles  which  resist  for  a  long  time  the  action  of  water. 

We  have  also  studied  the  effect  produced  by  shaking  with  quick-silver 
blood  to  which  various  reagents  have  been  added.  The  addition  of  con- 
centrated solutions  of  common  salt,  sulphate  of  magnesium,  sulphate  of 
sodium,  sulphate  of  zinc,  acetate  of  lead  and  sugar  has  no  appreciable  in- 
fluence upon  the  result  as  above  described.  On  the  other  hand  after  the 
addition  to  the  blood  of  solutions  of  pyrogallic  acid,  tannin,  alcohol,  chlorate 
of  potash,  nitrate  of  silver,  and  sulphate  of  copper,  the  red  blood-corpuscles 
are  unaffected  by  shaking,  no  matter  how  long  this  be  continued.  It  is  not 
necessary  to  describe  here  the  action  upon  the  red  blood-corpuscles  of  the 
various  reagents  in  the  latter  group.  This  has  already  been  described  by 
various  investigators.  We  used  strong  alcohol,  pyrogallic  acid  in  30^  solu- 
tion, tannin  and  sulphate  of  copper  in  10^,  chlorate  of  potash  in  6.25^ 
(1:16  the  maximum  of  its  solubility  at  tlie  ordinary  temperature)  and 
nitrate  of  silver  in  3^  solution.  Two  parts  of  the  solution  were  added  to  one 
part  of  the  blood.  As  regards  the  formation  of  shadows,  the  blood-corpuscles 
are  affected  but  little  by  the  first  three  reagents  and  not  at  all  by  the  last 
three.  No  matter  how  long  the  shaking  be  continued,  the  blood-corpuscles 
remain  unaffected  by  it.    The  experiments  were  frequently  repeated,  always 


46  BEHAVIOUR  OF  RED  BLOOD-CORPUSCLES 

with  a  control-specimen,  and  always  with  the  same  result.  With  some  of 
these  reagents  (chlorate  of  potash,  pyrogallic  acid  and  nitrate  of  silver)  we 
have  shaken  the  blood  over  two  weeks.  The  blood-corpuscles  appeared  as 
intact  at  the  end  as  at  the  beginning  of  the  experiment.  It  is  hardly 
necessary  to  add  that  under  tliese  circumstances  solution  of  the  haemoglobin 
does  not  occur  upon  allowing  the  blood  to  stand  after  it  has  been  shaken. 

As  no  change  was  produced  by  shaking  the  blood  for  two  weeks  it  did  not 
seem  necessary  to  continue  the  procedure  any  longer.  The  effect  of  these 
reagents  does  not  seem  to  be  merely  an  increase  in  the  cohesion  of  tlie  red 
blood-corpuscles.  In  fact  sugar  and  sulphate  of  sodium  are  credited  with 
the  power  of  hardening  the  red  blood-corpuscles,"  and  in  our  experiments 
these  substances  were  without  influence.  The  reagents  of  the  active  group 
must  produce  some  change  in  the  constitution  of  the  red  blood-corpuscles 
which  renders  them  wholly  insusceptible  to  such  mechanical  influences  as 
we  employed.  The  different  substances  of  this  group  have  as  approximately 
common  properties,  (a)  the  power  of  coagulating  albumen,  and  (6)  the 
power  of  changing  haemoglobin  into  meta-haemoglobin.  "We  content  our- 
selves merely  with  reference  to  these  points,  as  the  subject  is  not  sufficiently 
matured  to  warrant  fuller  consideration. 

In  the  endeavor  to  discover  shadows  of  the  red  blood-corpuscles  in  the 
shaken  blood  we  found  tlie  reagents  customarily  recommended  little  adapted 
for  this  purpose.  These  reagents  themselves  transform  blood-corpuscles  into 
shadows,  and  moreover  tliey  are  of  little  service  when  the  shadows  are  very 
pale  and  the  fluid  turbid.  Wliile  the  idea  previously  seems  to  have  been  to 
demonstrate  the  shadows  by  means  of  colouring  agents  (eosin,  vesuvin,  etc.), 
we  have  found  that  oilier  reagents  are  more  suitable.  It  would  seem  that 
all  reagents  which  cause  a  coagulation  of  albumen  are  adapted  to  render 
visible  the  palest  stromata.  We  have  used  successfully  for  this  purpose 
picric  acid  (saturated  solution),  pyrogallic  acid  {20'/(^),  bichromate  of  pot- 
ash (2^)  tannin  (10;^),  sulphate  of  copper  (10;^),  nitrate  of  silver  (3^), 
chlorate  of  potash  (1 :  16)  and  diluted  mineral  acids.  The  stromata  appear 
after  the  addition  of  these  reagents  in  a  few  seconds  as  pale  rings,  except  in 
the  case  of  chlorate  of  potash,  which  makes  them  appear  as  bluish-white 
round  discs.  The  clearest  outlines  are  produced  by  picric  acid,  pyrogallic 
acid,  chlorate  of  potash  and  nitrate  of  silver.  The  first  two  reagents  are, 
however,  not  adapted  for  the  study  of  normal  blood,  as  they,  like  most  of 
the  other  reagents,  cause  more  or  less  separation  of  haemoglobin.  On  the 
other  hand,  nitrate  of  silver  and  chlorate  of  potash  are  admirable  reagents 
for  the  purpose  in  view.  If  two  parts  of  the  reagent  (of  the  before  men- 
tioned concentration)  be  mixed  with  one  part  of  blood,  then  the  shadows 
come  plainly  to  view  while  the  intact  corpuscles  remain  unchanged. 

'  Joh.  Miiller:    Hand.  d.  Physiol.  Figuera,  Ann.  d.  Cliim.  u.  Phys.  XL. 


THE  STRUCTUEE  OF  WHITE  THKOMBr 

A  year  ago,  upon  an  occasion  similar  to  this,  you  had  the  pleasure  of 
listening  to  Dr.  J,  Collins  Warren's  address  upon  the  healing  of  arteries 
after  ligature.  As  his  researches  were  directed  especially  toward  the  later 
stages  of  the  changes  which  follow  injury  of  the  bloodvessels,  it  will,  perhaps, 
not  be  acceptable  if  I  call  your  attention  to  the  histological  structure  of  those 
plugs  which  often  constitute  the  earliest  alteration  following  such  injury. 

While  all  that  pertains  to  the  subject  of  thrombosis  is  of  importance, 
recent  investigations  have  lent  special  interest  to  the  study  of  the  minute 
structure  and  the  mode  of  formation  of  white  thrombi. 

Since  Virchow's  memorable  publications '  upon  the  subject  of  thrombosis, 
it  has  been  generally  believed  that  a  thrombus  is  essentially  a  blood  coagu- 
lum,  and  differs  from  an  ordinary  post-mortem  clot  only  in  the  arrangement 
and  the  relative  proportion  of  the  constituent  histological  elements.  The 
most  important  of  the  differences  noted  by  Virchow  are  the  characteristic 
lamination  of  thrombi,  and  their  greater  richness  in  white  blood-corpuscles, 
and  in  granular  material.  These  differences  were  believed  to  be  sufficiently 
explained  by  the  slow  formation  of  thrombi  from  the  circulating  blood,  in 
contrast  with  the  rapid  coagulation  of  blood  at  rest,  and  by  secondary  changes 
in  the  thrombus. 

During  the  two  decades  following  the  publication  of  Virchow's  researches 
on  this  subject,  more  attention  was  paid  to  the  causes,  to  the  effects,  and 
to  the  metamorphoses  of  thrombi,  more  particularly  to  their  so-called  organi- 
zation, than  to  the  intimate  structure  of  recently  formed  thrombi.  Zahn's 
investigations  of  thrombosis,  published  in  1875,  marked  an  epoch  in  the 
history  of  our  subject.*  Zahn  had  been  preceded  by  Mantegazza,*  who,  in 
1869,  called  attention  to  the  role  played  by  white  blood-corpuscles  in  the 
formation  of  white  thrombi,  but  the  observations  of  the  latter  author  had 
remained  comparatively  unknown. 

Zahn  emphasized  the  most  important  differences  existing  between  thrombi 
formed  from   the  blood  in  repose,  the  so-called  red   thrombi,  and  those 

'  Delivered  before  the  Pathological  Society  of  Philadelphia,   April  28,  1887. 

Tr.  Path.  Soc,  Phila.,  1885-7,  XIII,  281-300. 
=  Virchow:    Gesammelte  Abhandlungen.     Frankfurt  a.  M.,  1S56. 
'Zahn:     Virchow's  Archiv,  1875,   Bd.  62,  p.  81. 
*  Mantegazza:    Gaz.  med.  Lombarda,  1869. 

47 


48  STRUCTUEE  OF  WHITE  THROMBI 

developed  from  circulating  blood,  viz.,  the  white  and  the  mixed  thrombi. 
WTiereas  the  former  do  not  differ  from  an  ordinary  coagulum  of  blood,  the 
latter,  according  to  Zahn,  originate  from  clumps  of  white  corpuscles.  Zahn 
observed  miscroscopically  in  the  mesenteric  vessels  of  the  living  frog,  the 
first  formation  of  white  thrombi  out  of  wliite  blood-corpuscles  which  accu- 
mulated in  vessels  at  places  which  had  been  subjected  to  various  injuries. 
The  white  corpuscles  thus  accumulated,  if  they  were  not  detached  by  the 
circulation,  rapidly  disintegrated  into  a  mass  of  granular  material  which 
Zahn  considere(;l  to  be  granular  fibrin.  According  to  the  widely  accepted 
views  of  Zahn,  therefore,  a  white  thrombus  at  its  inception  consists  essentially 
of  white  blood-corpuscles,  which,  after  a  short  time,  break  up  into  a  mass 
of  granules  identical  with  fibrin  in  their  reactions. 

The  observations  of  Mantegazza  and  of  Zahn  were  confirmed,  in  1876, 
by  Pitres,'  who  made  corresponding  observations  of  the  living  circulation  in 
warm-blooded  animals,  whereas  Zahn  studied  the  circulation  only  in  frogs. 
Pitres,  however,  did  not,  like  Zahn,  identify  the  granular  material  resulting 
from  the  disintegration  of  white  blood-corpuscles  with  fibrin. 

The  role  thus  assigned  to  the  white  corpuscles  in  the  formation  of  white 
thrombi  certainly  seemed  to  be  at  variance  with  Virchow's  view  that  all 
thrombi  are  coagula.  A  reconciliation,  however,  was  effected  between  the 
new  observations  and  the  old  doctrine,  chiefly  through  the  investigations  of 
Weigert.'  This  pathologist,  adopting  the  views  of  A.  Schmidt  as  to  the  part 
taken  by  the  white  corpuscles  in  the  spontaneous  coagulation  of  the  blood, 
assigned  to  these  corpuscles  essentially  the  same  role  in  white  thrombi. 
The  coagulation  necrosis  of  leucocytes  in  thrombi  is  a  process  differing, 
according  to  Weigert,  morphologically,  but  not  in  essence,  from  the  dissolu- 
tion of  white  corpuscles  and  the  formation  of  fibrillated  fibrin  in  the 
ordinary  coagulation  of  the  blood.  White  thrombi,  therefore,  continued  to 
be  regarded  as  in  the  main  genuine  coagula. 

The  first  opposition  to  the  views  of  Zahn  came  from  Hayem,'  who.  in 
1878,  attempted  to  prove  that  the  coagulation  of  fibrin  is  a  function  of  the 
small  bodies,  called  by  him  haematoblasts,  and  subsequently,  by  Bizzozero, 
blood  plates,  the  name  now  generally  adopted.  Osier,  who  was  among  the 
first  to  observe  the  existence  of  human  thrombi  composed  almost  exclusively 
of  blood  plates  (or  plaques,  as  he,  accepting  the  suggestion  of  Kemp,  prefers 

» Pitres:    Arch,  de  Phys.  norm,  et  path.,  1876,  p.  230. 

'Weigert:  Virchow's  Archiv,  Bd.  70,  1877,  and  Bd.  79,  1880.  Fortschritte  d. 
Medicin,  1883. 

'Hayem:  Recherches  sur  I'Anatomie  norm,  et  path,  du  Sang.  Paris,  1878. 
Comptes  Rendus  de  I'Acad.  d.  Sc,  1882,  18  Juli. 


STRUCTUEE  OF  WHITE  THEOMBI  49 

to  call  them),  has  presented  fully  in  the  last  series  of  Cartwright  Lectures, 
the  existing  state  of  our  knowledge  concerning  these  bodies.'  In  1882, 
Hayem  published  his  observations  on  the  structure  of  thrombi.  He  found 
that  the  thrombi  which  are  formed  in  wounds  of  arteries  are  made  up  of 
blood  plates. 

A  few  months  later  Bizzozero '  described,  with  much  detail,  both  the 
fibrin-forming  properties  of  the  blood  plates,  and  their  presence  as  the 
essential  and  primary  constituent  of  white  thrombi,  in  these  respects  con- 
firming the  opinions  of  Hayem.  Bizzozero  was  the  first  to  study  the  forma- 
tion of  thrombi  from  blood  plates  in  the  living  circulation,  usuing  for  thlB 
purpose  the  mesenterj'  of  warm-blooded  animals. 

In  the  following  year,  Hlava,"*  working  under  Weigert's  direction,  was 
unable  to  confirm  the  views  of  Hayem,  and  of  Bizzozero,  and  upheld  the 
doctrine  of  Zahn  and  of  Weigert,  that  white  thrombi,  in  their  earliest  forma- 
tion, consist  mainly  of  leucocytes,  which  subsequently  undergo  coagulation 
necrosis. 

Lubnitzky,"  working  under  the  direction  of  Langhans,  published,  in  1885, 
an  interesting  article,  in  which  she  claimed  that  the  thrombi  which  are 
formed  in  arterial  wounds,  and  which  are  the  chief  agent  of  nature  in 
checking  hemorrhage  from  this  source,  are  composed  primarily  of  blood 
plates.  The  blood  plates,  when  thus  accumulated,  are,  according  to 
Lubnitzky,  either  identical  with  fibrin,  or  are  quickly  transformed  into 
this  substance. 

The  most  thorough  study  hitherto  made  of  the  share  taken  by  the  blood 
plates  in  the  formation  of  thrombi  we  owe  to  Ebertli  and  Schimmelbusch. " 
These  authors  consider  that  sufficient  proof  of  the  existence  of  blood  plates 
in  the  normal  circulation  is  afforded  by  the  observation  of  the  plates  in  the 
circulating  blood  of  the  mesenteric  vessels  of  dogs  and  rabbits  examined 
under  physiological  salt  solution,  with  high  magnifying  powers.  In  opposi- 
tion to  Hayem  and  to  Bizzozero,  they  deny  that  the  plates  have  any  share  in 
the  coagulation  of  fibrin,  which  they  regard  rather  as  a  kind  of  crystalli- 
zation in  the  plasma.  The  plates,  when  removed  from  the  natural  conditions 
of  their  existence,  rapidly  undergo  a  metamorphosis,  called  by  Eberth  and 
Schimmelbusch  viscous  metamorphosis,  and  characterized  especially  by  the 

'Osier:  On  Certain  Problems  in  the  Physiology  of  the  Blood  Corpuscles. 
The  Medical  News,  April  3,  10,  17,    1886. 

"Bizzozero:     Virchow's   Archiv,   1882,  Bd.  90,  p.  261. 

"Hlava:    Arch.  f.  exp.  Path.  u.  Pharm.,  1883,  Bd.  17,  p.  392. 

"  Lubnitzky:    Arch.  f.  exp.  Path.  u.  Pharm.,  1885,  Bd.  19,  p.  185. 

"Eberth  u.  Schimmelbusch:  Virchow's  Archiv,  1885,  Bd.  101;  1886,  Bd.  103, 
Bd.  105. 


50  STRUCTURE  OF  WHITE  THROMBI 

sticking  of  the  plates  to  each  other  and  to  foreign  substances.  Under  normal 
conditions  the  plates  circulate  with  the  red  corpuscles  in  the  axial  blood 
current,  but  they  make  their  appearance  in  the  plasmatic  zone  when  the 
rapidity  of  the  circulation  is  diminished.  A  moderate  slowing  of  the  blood 
current  is  attended  by  the  formation  of  the  so-called  border  zones,  or  accumu- 
lation of  white  corpuscles  in  the  plasmatic  current,  whereas  a  greater 
diminution  of  the  velocity  of  the  stream  is  characterized  by  fewer  leucocytes, 
and  more  plates  in  the  peripheral  current.  Other  irregularities  of  the 
circulation,  such  as  the  little  eddies  produced  by  obstacles  or  projections  in 
the  stream,  or  by  dilatations  of  its  bed,  may  likewise  throw  the  plates  from 
the  axis  into  the  periphery  of  the  stream.  Mere  slowing  of  the  circulation 
is  not  attended  by  the  formation  of  thrombi.  In  order  to  observe  this 
formation,  Eberth  and  Schimmelbusch  subjected  the  living  mesenteric 
vessels,  chiefly  of  dogs,  to  various  mechanical  and  chemical  injuries.  They 
then  ol>served  under  the  microscope,  in  many,  but  not  in  all  instances,  the 
accumulation  of  blood  plates  at  the  seat  of  injury.  Here  the  plates  became 
adlierent  to  each  other  and  to  the  wall  of  the  vessel,  in  consequence  of  their 
viscous  metamorphosis,  and  thus  formed  plugs  which  were  often  subsequently 
washed  away,  but  which  sometimes  increased  in  size  so  as  to  obstruct  com- 
pletely the  lumen  of  the  vessel.  Red  and  white  corpuscles  may  be  included 
in  the  mass  of  plates,  but  their  presence  is  purely  accidental,  and  they  are  not 
to  be  regarded  as  an  essential  constituent  of  the  primary  thrombus. 

As  the  result  of  their  microscopical  observations  of  the  formation  of 
thrombi  in  living  bloodvessels  of  warm-blooded  animals,  Eberth  and 
Schimmelbusch,  therefore,  conclude  that  white  thrombi  are  at  first  com- 
posed essentially  of  blood  plates,  and  that  the  chief  factors  in  the  causa- 
tion of  such  thrombi  are  slowing  of  the  circulation  or  other  irregularities 
in  tlie  current,  and  the  viscous  metamorphosis  of  the  blood  plates.  This 
metamorphosis  may  be  the  result  of  various  influences,  such  as  contact  with 
injured  or  diseased  vascular  walls  and  with  foreign  substances. 

These  conclusions  as  to  the  structure  of  white  thrombi  at  their  earliest 
formation  Eberth  and  Schimmolbusch  confirmed  by  the  microscopical 
examination  of  sections  of  thrombi  produced  artificially  by  various  injuries 
to  the  vessels.  In  experimental  thrombi  produced  by  meclianical  injury  of 
the  vessels,  as  by  wounds  or  by  temporary  ligation,  they  failed  to  find  any 
fibrillated  fibrin,  whereas,  in  thrombi  formed  around  foreign  bodies  intro- 
duced into  the  lumen  of  a  bloodvessel,  they  observed  some  fibrin,  situated 
usually  between  masses  of  plates,  although  even  here  they  think  it  probable 
that  fibrin  is  absent  in  the  very  earliest  stages.  They  also  detected  fibrin, 
but  in  less  amount,  in  thrombi  produced  by  cauterization  of  the  vessel  walls. 


STEUCTURE  OF  WHITE  THROMBI  51 

While  the  investigations  of  Eberth  and  Schimmelbuseh  confirm  the  view 
of  Hayem,  Bizzozero,  and  Lubnitzky  that  w^hite  thrombi  are  made  up  pri- 
marily of  an  accumulation  of  blood  plates  and  not  of  leucocytes  as  Zalm  had 
led  us  to  believe,"  they  are  opposed  in  one  important  particular  to  the  con- 
clusions of  the  latter  group  of  authors.  They  deny  that  the  blood  plates  are  in 
any  vray  concerned  in  the  generation  of  fibrin  or  are  transformed  into  a  sub- 
stance resembling  fibrin.  They,  therefore,  deny  that  a  wliite  thrombus  is 
primarily  a  coagulum,  as  has  hitherto  been  unquestionably  believed.  They 
regard  the  process  of  thrombosis,  here  under  consideration,  as  a  conglutinor- 
tion  of  bodies  preexistent  in  the  blood  and  not  as  a  coagulation. 

The  arguments  brought  forward  by  the  preceding  investigators  in  favor 
of  the  existence  of  blood  plates  in  large  number  in  the  normal  circulation, 
convincing  as  they  may  seem,  are  nevertheless  opposed  by  several  observers. 
In  view  of  the  researches  of  Lowit,"  this  must  for  the  present  be  considered 
as  an  open  question. 

Xotwithstanding  the  brief  period  which  has  elapsed  since  the  publication 
of  Eberth  and  Scliimmelbusch's  researches  upon  thrombosis,  their  con- 
clusions have  already  met  with  considerable  opposition.  It  was  hardly  to 
be  expected  that  such  a  radical  overturning  of  accepted  beliefs  as  these 
recent  investigations  involve  should  pass  unchallenged. 

While  there  is  general  agreement  of  opinion  as  to  the  important  par- 
ticipation of  blood  plates  in  the  composition  of  white  thrombi,  Eberth  and 
Scliimmelbusch's  conception  of  the  process  of  thrombosis  as  a  conglutination 
of  blood  plates  which  have  undergone  a  viscous  metamorphosis  is  opposed 
by  Hanau"  on  the  ground  that  thrombi  never  have  a  viscid  consistence. 
In  support  of  the  coagulative  nature  of  the  accumulation  and  metamorphoses 
of  blood  plates  in  white  thrombi  Hanau  finds  that  plates  as  well  as  fibrin 
are  transformed  into  hyaline,  that  a  rim  of  hyaline  forms  around  masses 

"  Since  the  delivery  of  this  address  Eberth  and  Schimmelbuseh  have  pub- 
lished the  results  of  their  repetition  of  Zahn's  experiments  on  the  mesenteric 
vessels  of  frogs,  and  they  find  that  fusiform  corpuscles,  which  they  consider  to 
correspond  to  the  mammalian  blood  plates,  are  the  main  constituents  of  white 
thrombi  artificially  produced  in  these  animals.  Vide  Virchow's  Archiv,  Bd. 
108,  1887.  Lowit,  on  the  other  hand,  regards  these  fusiform  corpuscles  as  a 
variety  of  the  white  corpuscles  and  not  as  the  analogues  of  blood  plates,  and 
he  confiirms  the  original  statements  of  Zahn  regarding  the  tormation  of 
white  thrombi  in  frogs.    Archiv  f.  exp.  Path.  u.  Pharm.,  Bd.  23,  1887. 

"Lowit:  Beitrage  z.  Lehre  von  d.  Blutgerinnung,  Sitzb.  d.  k.  Akad.  d.  Wiss. 
Wien,  Bd.  89,  Abth.  Ill,  u.  Bd.  90,  Abth.  Ill,  and  Tageblatt  d.  59ter  Versaml 
Deutscher  Naturforscher  u.  Aertze  in  Berlin,  p.  306,  1886. 

''Hanau:    Fortschritte  der  Medicin,  No.  3,  1887. 


52  STRUCTUEE  OF  WHITE  THROMBI 

of  plates,  and  that  fibrin  and  plates  often  take  the  place  one  of  the  other 
in  thrombi. 

Weigert "  protests  even  more  vigorously  against  the  effort  of  Eberth  and 
Schimmelbusch  to  remove  a  large  class  of  thrombi  from  the  categor}'  of 
coagula.  He  has  made  a  careful  examination  of  human  white  thrombi, 
and  points  out  especially  their  richness  in  fibrillated  fibrin,  which  he 
demonstrates  by  a  new  staining  process,  and  the  abundance  of  leucocytes. 
He  is  unable  to  identify  these  anatomical  thrombi  with  the  experimental 
tlirombi  of  Eberth  and  Schimmelbusch,  and  argues  that  until  some  reconcili- 
ation is  effected  between  the  two  we  should  continue  to  base  our  conception 
of  the  nature  of  thrombi  upon  the  study  of  the  anatomical  thrombi.  Eberth 
and  Schimmelbusch  reply  that  their  studies  have  been  directed  to  the  very 
earliest  stages  of  the  process  of  thrombosis,  whereas  the  thrombi  examined 
by  Weigert  belonged  to  subsequent  metamorphoses,^' 

It  is  apparent  from  the  foregoing  review  of  recent  investigations  con- 
cerning the  nature  and  structure  of  thrombi  that  unanimity  of  opinion 
on  this  subject  has  not  been  reached.  There  is  general  agreement  that  the 
blood  plates  play  an  important  role  in  the  early  formation  of  many  thrombi. 
Further  investigations  are  needed  to  determine  whether  or  not  the  plates 
are  present  in  the  perfectly  normal  circulation.  For  a  proper  understanding 
of  the  process  of  thrombosis  it  is  important  to  determine  whether  or  not 
the  blood  plates  when  accumulated  to  form  a  thrombus,  are  products  of 
coagulation  or  subsequently  undergo  any  metamorphosis  which  can  be  called 
coagulation.  To  determine  this  the  gross  characters  of  the  plate  thrombi, 
such  as  their  color  and  consistence,  will  serve  as  important  criteria,  as  has 
been  pointed  out  by  Weigert.  It  is,  of  course,  of  capital  importance  to  learn 
whether  the  experimental  wliite  thrombi  differ  in  their  nature  from  human 
thrombi  as  seems  to  be  intimated  by  Weigert.  Before  far-reaching  con- 
clusions can  be  drawn  it  is  necessary  to  demonstrate  the  identity  of  the 
experimental  and  of  the  anatomical  process  of  thrombosis.  The  micro- 
scopical study  of  human  thrombi  certainly  seems  opposed  to  tlie  opinion  that 
fibrin  and  leucocytes  are  unessential  constituents  of  white  thrombi.  So 
constant  and  so  abundant  are  these  elements  in  post-mortem  white  thrombi 
that  pathological  anatomists  will  not  readily  admit  that  their  presence  is 

'•Weigert:  Tageblatt  der  59ter  Versamml.  Deutscher  Naturforscher  u.  Aerzte 
In  Berlin,  p.  306,  1886. 

"Schimmelbusch:  Tageblatt  d.  59ter  Versamml.  Deutscher  Naturforscher  in 
Berlin,  p.  306,  1886.  Eberth  u.  Schimmelbusch,  Fortschritte  der  Medicin,  No.  6, 
1887.  The  paper  of  Lbwit,  on  thrombosis,  who  is  opposed  in  many  important  par- 
ticulars to  Eberth  and  Schimmelbusch,  appeared  after  the  delivery  of  this 
address.    Arch.  f.  exp.  Path.  u.  Pharmak.  Bd.  22,  1887. 


STRUCTURE  OF  WHITE  THROMBI  53 

accidental  or  unessential  to  our  conception  of  the  nature  of  the  thrombotic 
process. 

In  view  of  the  fundamental  importance  of  the  question  last  touched  upon, 
I  have  undertaken  some  investigations,  first,  as  to  the  structure  of  human 
wliite  thrombi ;  and  second,  as  to  the  structure  of  thrombi  produced  experi- 
mentally in  animals  by  mechanical  injury  of  the  bloodvessels.  In  the 
study  of  experimental  thrombi  I  have  directed  my  attention,  in  the  first 
place,  to  their  constitution  at  their  earliest  formation,  and  especially  to  the 
presence  or  absence  of  fibrin  and  of  leucocytes  at  this  period.  It  has  seemed 
to  me  that  a  control  with  reference  to  the  latter  point  of  observations  of 
Hayem,  Bizzozero,  Lubnitzky,  and  especially  of  Eberth  and  Schimmel- 
busch,  notwithstanding  the  carefulness  of  these  observations,  might  not  be 
unwelcome.  I  have  also  studied  the  structure  of  experimental  thrombi  in 
their  later  stages.  It  is  undoubtedly  upon  this  point  that  our  knowledge  is 
the  least  complete,  and  it  is  to  be  expected  that  when  this  gap  is  filled  up 
there  will  be  less  divergence  of  opinion  as  to  the  relation  between  the  experi- 
mental and  the  human  thrombi. 

There  will  be  found  on  exhibition  under  the  microscopes  sections  of 
human  marantic  thrombi  formed  in  various  infectious  and  wasting  diseases. 
Among  others  specimens  are  present  from  a  case  of  widespread  thrombosis 
following  parturition.  In  this  case  there  were  fresh  thrombi  in  the  femoral 
and  iliac  veins,  the  inferior  vena  cava,  the  branches  of  the  pulmonary 
artery,  and  the  cerebral  sinuses.  The  constituent  elements  of  these  thrombi 
are  fibrillated  fibrin,  hyaline  substance,  red  blood-corpuscles,  leucocytes, 
fragmented  nuclei,  and  granular  material,  of  which  a  considerable  part  can 
be  recognized  as  blood  plates.  The  proportion  of  each  of  these  elements  in 
the  composition  of  thrombi  varies  much  in  different  cases,  and  it  will  be 
well  to  consider  the  share  taken  by  each  in  the  formation  of  thrombi. 

There  have  been  various  opinions  as  to  the  nature  of  the  granular  material 
found  in  thrombi.  Thus  it  has  been  regarded  as  produced  by  the  breaking 
up  of  fibrillated  fibrin  (Virchow),  as  molecular  or  granular  fibrin  deposited 
as  such  from  the  blood — a  view  advocated  by  the  majority  of  the  older 
(Mandl,  Addison)  and  by  many  recent  authors — as  granular  fibrin  formed 
by  the  necrosis  of  white  corpuscles  (Zahn),  as  the  result  of  simple  disintegra- 
tion of  white  corpuscles  (Pitres).  At  present,  however,  there  can  be  no 
doubt  that  most  of  what  has  been  called  in  thrombi  granular  fibrin,  or  the 
products  of  disintegration  of  leucocytes,  consists  of  more  or  less  altered  blood 
plates.  The  acquisition  of  this  knowledge  is  an  important  advance  in 
pathology,  whatever  may  be  thought  of  the  nature  of  the  plates. 

Blood  plates  seem  to  be  a  constant  constituent  of  fresh  marantic  thrombi. 
The  plates  are  often  present  in  such  thrombi  in  as  recognizable  form  and 


54  STRUCTURE  OF  WHITE  THROMBI 

arrangement  as  in  recent  experimental  thrombi.  I  have  found  thrombi, 
particularly  some  endocardial  vegetations  and  parietal  arterial  thrombi, 
which  at  first  glance  appear  to  be  composed  of  nothing  but  plates;  but 
careful  examination  in  such  cases  has  always  revealed  the  presence  also  of 
fibrillated  fibrin  and  leucocytes.  In  the  majority  of  cases,  however,  the  part 
of  the  thrombus  composed  of  plates  is  less  extensive  then  that  made  up  of 
fibrin  and  leucocytes.  Frequently  the  plates  are  arranged  in  massed  between 
which  lie  the  fibrin  and  leucocytes.  Such  masses  of  plates,  which  are  more 
frequently  situated  in  the  interior  of  the  thrombus  than  adjacent  to  the 
vessel-wall,  are  often  enveloped  in  a  rim  of  dense  material  resembling  fibrin. 
In  sections  stained  with  hnematoxylin  and  eosin  the  areas  occupied  by  the 
plates  can  often  be  recognized  with  a  low  power  by  the  various  manner  in 
which  the  different  constituents  of  the  thrombus  stain. 

All  of  the  granular  material  in  thrombi  cannot  be  demonstrated  to  be 
composed  of  plates,  but  it  is  probable  that  most  of  this  formless  granular 
matter  is  the  result  of  the  disintegration  and  metamorphosis  of  the  plates. 
That  some  of  the  granules  are  produced  by  the  disintegration  of  leucocytes 
is  probable,  for  it  is  not  difficult  to  demonstrate  the  destruction  of  leucocytes 
in  many  thrombi.  I  believe  also  that  a  granular  precipitate  in  thrombi 
is  sometimes  caused  by  the  hardening  agents. 

As  regards  fibrin,  I  can  confirm  the  recent  statements  of  Weigert  as  to 
the  abundance  and  the  constant  presence  of  this  substance  in  all  marantic 
thrombi,  except  in  softened  foci  where  it  is  absent.  Some  thrombi  are  com- 
posed almost  wholly  of  fibrin.  The  fibrin  may  assume  various  forms,  such 
as  the  form  of  a  delicate  network,  or  of  coarse  interlacing  or  parallel  bands, 
or  of  irregular  masses,  or  of  the  so-called  canahzed  fibrin.  In  sufficiently 
thin  sections,  such  as  can  be  made  from  specimens  imbedded  in  paraffine, 
there  is  generally  no  difficulty  in  demonstrating  in  thrombi  a  rich  network 
of  fibrin  even  without  the  aid  of  Weigert's  special  stain  for  this  purpose. 
Leaving  out  of  question,  therefore,  the  nature  of  tlie  blood  plates,  there  can 
be  no  doubt  that  human  thrombi,  as  we  meet  them  at  autopsies,  are  genuine 
coagula,  save  in  the  foci  of  so-called  puriforra  softening. 

Hyaline  material  appears  to  be  formed  both  out  of  fibrin  and  out  of 
blood  plates.  Tliroml)i  composed  wholly  of  hyaline  I  have  found  in  the 
liver  of  a  cat  in  which  a  few  drops  of  croton-oil  had  been  injected,  in 
hemorrhagic  infarctions  of  the  lungs,  and  in  corroding  ulcers  of  the  duo- 
denum and  of  the  stomach.  Hyaline  is  an  inconstant  constituent  of  thrombi, 
but  its  presence  is  not  rare. 

The  accumulation  of  leucocytes  in  human  white  thrombi  is  so  well  known 
that  tliere  would  be  no  necessity  of  emphasizing  it  here,  were  it  not  that  the 
recent  study  of  experimental  thrombi  has  led  to  a  revision  of  the  doctrine 


STEUCTURE  OF  WHITE  THROMBI  55 

that  white  tlirombi  are  composed  primarily  of  masses  of  white  blood- 
corpuscles.  While  it  is  true,  as  has  already  been  mentioned,  that  there  are 
thrombi  which  are  composed  almost  entirely  of  plates,  or  of  fibrin,  or  of 
hyaline,  or  of  these  substances  in  combination,  this  is  the  exception,  and  in 
the  vast  majority  of  fresh  thrombi  leucocytes  are  present  in  large  number. 
In  inflammatory  thrombi  leucocytes  may  be  so  abundant  as  to  obscure  all 
other  constituents.  Usually  the  leucocytes  in  marantic  thrombi  are  not 
scattered  uniformly  throughout  the  thrombus,  but  are  massed  together  in 
clumps;  these  clumps  of  leucocytes,  imlike  the  clumps  of  plates,  are  generally 
pervaded  by  a  network  of  fibrin. 

It  is  not  at  all  infrequent  to  find  in  old  thrombi  leucocytes  and  even 
masses  of  them  which  are  devoid  of  nuclei.  In  undergoing  this  necrosis 
the  nuclei  of  the  white  blood-corpuscles  may  be  broken  up  into  fragments 
which  can  be  recognized  as  small  irregular  particles  which  assume  a  nuclear 
staining,  but  this  nuclear  fragmentation  does  not  seem  to  be  the  rule.  Gen- 
erally the  necrotic  leucocytes  can  be  recognized  simply  by  their  form,  without 
any  trace  of  nuclei. 

Red  corpuscles  are  present  in  variable  numbers  in  marantic  thrombi. 
They  cannot  be  regarded  as  an  essential  constituent  of  the  thrombus.  I  find 
in  many  marantic  thrombi  the  so-called  shadows  of  the  red  blood-corpuscles, 
which  can  be  easily  overlooked  unless  especial  attention  be  given  to  search- 
ing for  them. 

In  properly  prepared  sections  it  is  not  rare  to  find  colonies  of  micrococci 
even  in  tlirombi  not  connected  with  pyaemic  processes,  especially  in  marantic 
thrombi  from  cases  of  typhoid  fever  or  other  infectious  diseases. 

From  the  foregoing  summar}^  of  the  histological  characters  of  human  white 
thrombi,  it  is  apparent  that  any  satisfactory  explanation  of  the  process  of 
thrombosis  must  account  for  the  presence  of  blood  plates,  of  fibrin,  and  of 
leucocytes,  for  these  are  essential  constituents  of  thrombi.  The  valuable 
investigations  by  Eberth  and  Schimmelbusch  of  experimental  thrombi  have 
led  theon  to  regard  the  blood  plates  as  the  sole  primary  elements  in  these 
plugs.  Further  investigations  are  needed  to  determine  the  role  played  by 
fibrin  and  white  blood-corpuscles  in  the  formation  of  experimental  thrombi. 

My  experiments  upon  the  production  of  thrombi  have  been  made  mostly 
on  dogs.  The  vessels  selected  have  been  the  femoral  artery,  the  femoral  vein, 
and  the  jugular  vein,  in  the  majority  of  cases  the  femoral  vessels.  Various 
methods  were  employed  to  produce  thrombi,  such  as  the  application  of 
caustics,  the  introduction  of  foreign  bodies,  and  various  mechanical  injuries. 
I  have  given  the  most  attention  to  the  thrombi  resulting  from  mechanical 
injuries,  for  it  is  admitted  by  Eberth  and  Schimmelbusch  that  the  thrombi 
following  the  application  of  caustics,  and  those  formed  around  foreign  sub- 


56  STRUCTURE  OF  WHITE  THROMBI 

stances,  contain,  in  an  early  stage,  if  not  at  their  beginning,  fibrin  as  well  as 
blood  plates.  These  authors  assert  that  "  coagulation  is  a  process  which 
plays  only  a  modest  role  in  tlie  circulating  blood,  whereas  here  the  most 
prominent  and  frequent  phenomenon  is  conglutination,  which,  indeed,  is 
solely  concerned  in  the  practically  most  important  form  of  thrombosis,  \\z., 
that  following  simple  mechanical  injury  of  the  vessel-wall,  in  whatever  way 
tliis  may  have  been  produced."  " 

The  follo^-ing  two  modes  of  producing  mechanically  thrombi  have  given 
good  results.  One  metliod  is  to  tie  a  stout  ligature  tightly  and  suddenly 
around  the  vessel  and  at  once  cut  the  ligature  loose.  In  this  way  the  intima 
and  a  part  of  the  media  are  usually  torn.  It  is  only  when  great  force  is  used 
that  the  vessel  is  ruptured.  The  ligature  leaves  a  whitish  ring  around  tlie 
vessel  at  the  seat  of  its  application.  If,  as  often  happens,  the  walls  of  the 
vessel  remain  stuck  together  after  removal  of  the  ligature,  then  moulding 
the  vessel  slightly  between  the  fingers  will  restore  the  lumen,  which  now 
presents  a  fusiform  dilatation  at  the  seat  of  injury.  The  adventitia  in  tliis 
situation  often  becomes  infiltrated  with  blood. 

Another  method  which  I  have  employed,  is  to  push  into  a  branch  of  the 
femoral  artery  or  femoral  vein  one  of  the  hooked  instruments  or  gouges  em- 
ployed by  dentists  and  called  excavators,  and  then,  after  pressing  the  hooked 
extremity  forward  into  the  main  trunk  to  scrape  the  inner  wall  of  the  vessel 
to  any  extent  desired.  The  stem  of  the  instrument,  if  necessary,  can  be  filed 
dowTi  so  as  to  render  its  introduction  easier.  After  the  withdrawal  of  the 
instrument  the  opened  branch  of  the  vessel  is  secured  by  two  ligatures.  Of 
the  various  shapes  which  the  working  extremities  of  these  instruments 
possess,  those  with  a  small  cup-shaped  gouge  bent  at  right  angles  to  the 
handle  (spoon  excavator)  I  have  found  particularly  suitable. 

The  animals  experimented  upon  have  been  tied  down  and  angestlietized, 
usually  with  morphine  and  chloral,  or  morphine  and  ether,  or  morphine 
alone. 

It  is  important,  when  the  vessel  is  removed  from  the  body,  that  four 
ligatures  sliould  be  applied,  two  above  and  two  below  the  seat  of  injury, 
and  that  any  collateral  branches  included  between  the  pairs  of  ligatures 
should  also  be  tied.  These  ligatures  should  be  applied  with  as  little  dis- 
turbance of  the  vessel  as  possible.  If  the  vessel  be  cut  out  without  the 
preliminary  application  of  ligatures,  the  contents  of  the  vessel  are  partly 
discharged,  and  in  this  way  the  thrombus  may  be  lost  or  its  position  changed. 

Various  hardening  fluids  were  employed,  such  as  corrosive  sublimate, 
alcohol,   Miiller's   fluid,  })!( ric  acid,  osmic  acid,  and  Flcmming's  solution. 

"Eberth  and  Schlmmelbusch.     Virchow's  Archlv,  Bd.  105,  p.  459. 


STRUCTURE  OF  WHITE  THROMBI  57 

Of  these,  warm  saturated  solutions  of  corrosive  sublimate  are  decidedly 
the  best.  This  fluid  preserves  the  blood  plates  and  other  elements  almost 
perfectly  and  admits  satisfactory  subsequent  staining  of  the  specimens. 

The  procedure  adopted  in  hardening  in  corrosive  sublimate  is  the  fol- 
lowing: A  clear,  saturated  aqueous  solution  containing  some  undissolved 
sublimate  at  the  bottom  is  heated  to  40°  C,  and  in  this  is  suspended  the 
specimen  to  be  hardened.  After  a  few  minutes  I  have  usually  cut  away 
the  ligatures  at  the  ends  of  the  vessel,  as  there  is  now  no  danger  of  the 
escape  of  the  contents.  The  vessel  containing  the  sublimate  solution  and 
specimen  is  kept  in  a  thermostat  at  a  temperature  of  40°  for  one  to  two 
hours.  The  specimen  is  then  washed  in  water  having  a  temperature  of 
40°  and  aftenvard  placed  in  a  mixture  of  half  alcohol  and  half  water,  and 
kept  in  this  mixture  at  a  temperature  of  40°  for  a  number  of  hours,  often 
over  night.  This  prolonged  washing  is  to  remove  cry-stals  which  other- 
wise are  present  in  large  number.  Even  after  this  treatment  sometimes 
peculiar  crystals  are  present,  which,  however,  do  not  materially  interfere 
with  the  study  of  the  sections.  The  addition  of  a  little  iodine  to  the 
washing  fluid,  as  suggested  to  me  by  Prof.  Gaule,  assists  in  removing  the 
crystals.  From  the  fifty  per  cent  alcohol  the  specimen  is  transferred  to 
strong,  and  finally  to  absolute  alcohol.  I  have  made  use  almost  exclu- 
sively of  paraffine  as  an  imbedding  medium,  as  much  thinner  sections 
can  be  obtained  in  this  way  than  by  imbedding  in  celloidine.  Satisfactory 
results  can  be  obtained  by  staining  the  specimens  en  masse  in  haematoxylin 
and  in  eosin,  but,  as  a  rule,  the  sections  have  been  stained  after  causing 
them  to  adhere  to  the  slide.  When  serial  sections  were  desired,  they  were 
cut  in  the  form  of  ribbons.  Gaule's  method  of  making  the  sections  adhere 
to  the  slide  by  placing  upon  each  section  laid  dry  upon  the  slide  a  drop 
or  two  of  forty  or  fifty  per  cent  alcohol,  and  after  ten  minutes  putting 
the  slides  in  a  thermostat  at  a  temperature  of  40°  and  keeping  them  there 
for  two  hours,  is  the  simplest  and  best  with  which  I  am  acquainted.  After 
this  treatment  the  sections  are  so  firmly  adherent  that  all  the  manipulations 
of  staining  and  preparing  the  sections  for  mounting  can  be  carried  on  with- 
out fear  of  their  detachment.  In  sections  stained  with  haematoxylin  and 
eosin  the  plates  have  a  violet  tint,  and  when  in  masses  can  be  readily  recog- 
nized with  a  low  power. 

I  wish  first  to  direct  your  attention  to  the  macroscopic  and  the  micro- 
scopic appearances  of  fresh  experimental  plate  thrombi.  Such  a  thrombus 
may  be  convieniently  produced  by  tying  forcibly  a  coarse  string  around 
the  femoral  arterj'  of  a  dog  and  then  at  once  cutting  the  string  loose  in  the 
manner  already  described.  After  the  time  desired  for  the  production  of 
the  thrombus  has  elapsed,  the  injured  part  of  the  artery  inclosed  between 
7 


58  STRUCTURE  OF  WHITE  THROMBI 

two  pairs  of  ligatures  is  to  be  removed  and  the  artery  is  to  be  carefully  slit 
up  with  a  pair  of  delicate  scissors. 

Let  us  examine  an  artery  treated  in  this  way  which  contains  a  thrombus 
formed  within  five  minutes.  There  will  be  found,  closely  adherent  to  the 
torn  inner  wall  of  the  vessel,  a  parietal  thrombus  which  at  this  period  does 
not  usually  extend  in  a  longitudinal  direction  much  beyond  the  ring  of 
lacerated  tissue.  The  thrombus  can  be  readily  distinguished  by  its  color 
from  the  blood  which  envelops  it  and  which  can  be  washed  away  with  salt 
solution.  The  thrombus  projects  irregularly  into  the  lumen  of  the  vessel, 
the  projecting  part  being  made  up  usually  of  round  or  irregular  masses 
which  are  connected  together. 

The  thrombus  has  a  homogeneous,  grayish,  translucent  appearance,  com- 
parable to  particles  of  boiled  sago,  and  resembling,  therefore,  the  color  of 
the  Malpighian  bodies  in  a  waxy  spleen.  \Yhen  bits  of  the  thrombus  are 
pressed  into  thin  layers  between  the  slide  and  the  cover-glass  they  present 
a  bluish  transparency  almost  glass-like.  The  epithet  hyaline  can  be  appro- 
priately applied  to  the  naked-eye  appearance  of  the  thrombus. 

The  consistence  of  the  thrombus  is  soft,  the  weight  of  the  cover-glass 
sufficing  to  make  bits  of  the  thrombus  spread  out  into  thin  layers.  In 
attempting  to  tease  apart  portions  of  the  thrombus,  it  is  found  that  this 
does  not  break  up  into  little  granules,  as  would  be  the  case  if  the  blood 
plates  which  compose  it  had  undergone  no  changes  and  were  simply  in 
apposition  to  each  other;  but,  on  the  other  hand,  the  thrombus  possesses 
considerable  cohesion,  and  in  breaking  it  into  fragments  with  teasing  needles 
fine  sticky  threads  can  be  drawn  out  a  short  distance  which  break  apart,  or, 
if  the  tension  be  removed,  retract.  Portions  of  the  thrombus  pressed  be- 
tween the  fingers  present  a  sticky,  gelatinous  consistence.  In  view  of 
Hanau's  objection,  already  mentioned,  to  Eberth  and  Schimmelbusch's 
designation  of  the  change  by  which  the  plates  adhere  to  each  other  as  a 
viscous  metamorphosis,  it  is  to  be  emphasized  that  fresh  plate  thrombi  have  a 
somewhat  viscid  consistence,  which  becomes  more  marked  in  the  course 
of  an  hour  after  the  removal  of  the  thrombus.  I  cannot,  therefore,  accept 
Hanau's  objection,  so  far  as  this  point  is  concerned,  as  valid. 

If  parts  of  the  fresh  thrombus  be  teased  in  physiological  salt  solution 
or  in  Bizzozero's  metliyl-violot  salt  solution,  or  in  Hayem's  solution,  there 
will  be  seen  masses  of  blood  plates  and  a  large  number  of  free  plates  floating 
in  the  liquid.  The  plates  appear  as  pale,  well  difl'erentiated,  round  or  some- 
what irregular  bodies  varying  in  size,  the  average  being  about  one-quarter 
the  diameter  of  a  red  blood-corpuscle.  Masses  of  plates  resemble  colonies 
of  large  micrococci.  They  can  be  made  to  assume  feeble  tints  with  a  variety 
of  coloring  agents,  but  I  have  not  been  able  to  give  them,  in  their  fresh 


STRUCTURE  OF  WHITE  THRO^IBI  59 

state,  a  sharp,  elective  staining.  In  water  the  plates  become  paler  and  some- 
what swollen ;  in  very  dilute  acetic  acid  they  become  darker  in  color  and  more 
distinct,  in  strong  acetic  acid  they  disappear  from  view. 

By  tapping  with  a  needle  upon  the  cover-glass  it  can  be  seen  that  the 
individuals  composing  the  masses  of  plates  adhere  to  each  other.  Such 
masses  may  be  readily  flattened  out  and  compressed.  The  plates,  espe- 
cially when  in  masses,  may  be  drawn  out  lengthwise  by  currents  of  fluid 
or  by  pressure.  The  remarkable  viscidity  of  the  plates  can  be  demonstrated 
by  placing  a  bit  of  filter  paper  at  the  edge  of  the  cover-glass  and  thus  causing 
currents  in  the  fluid  which  fail  to  draw  along  even  the  isolated  plates. 

In  order  to  see  the  regular  and  characteristic  appearance  of  the  fresh 
plates  when  arranged  in  masses,  it  is  necessary  that  they  should  not  be 
subjected  to  any  pressure.  When  masses  of  plates  are  compressed  even 
by  the  weight  of  the  cover-glass  they  often  appear  to  be  made  up  wholly 
or  in  part  of  pale  lines  instead  of  coarse  granules.  This  appearance  of 
lines  or  threads  seems  to  be  due  to  an  elongation  and  coalescence  of  the 
plates.  These  lines  are  often  arranged  with  considerable  regularity.  They 
might  be  mistaken  for  threads  of  fibrin.  A  similar  appearance  of  tlueads 
produced  by  coalescence  of  the  plates  is  sometimes  seen  in  hardened  speci- 
mens where  the  threads  are  often  varicose.  Whether  this  appearance  is 
due  to  the  action  of  the  hardening  agent  or  to  some  other  influence,  such 
as  the  force  of  the  circulating  blood,  must  be  left  unsettled. 

Although  the  plates  make  up  the  great  mass  of  the  thrombus  leuco- 
cytes are  present  even  at  this  early  stage  (during  the  first  five  minutes),  and 
rapidly  increase  in  number,  so  that  at  the  end  of  half  an  hour  the  throm- 
bus usually  contains  them  in  abundance.  My  investigations  have  not  led 
me  to  assign  so  insignificant  a  role  to  the  leucocytes  in  experimental 
thrombi  as  is  done  by  Eberth  and  Schimmelbusch.  I  agree  with  these 
authors  in  finding  that  thrombi  produced  mechanically  in  the  manner 
mentioned  consist  in  their  inception  essentially  of  blood  plates.  At  the 
end  of  five  minutes  the  leucocytes  may  be  so  scanty  as  not  to  attract  atten- 
tion. Usually,  however,  by  this  time  clumps  of  leucocytes  as  well  as  scat- 
tered leucocytes  are  present  here  and  there  in  the  thrombus,  and,  as  already 
mentioned,  their  number  continues  to  increase.  I  have  fomid  them  at  the 
end  of  six  hours,  in  mechanical  thrombi,  as  numerous  as  in  many  human 
marantic  thrombi.  It  is  true  that  much  diversity  exists  as  regards  the 
number  of  leucocytes  even  in  thrombi  of  the  same  age,  still  it  is  the  rule 
that  white  corpuscles,  while  they  do  not  collect  so  rapidly  or  in  such  num- 
ber as  the  blood  plates,  do  accumulate  and  form  a  constituent  part  of 
experimental  mechanical  thrombi.  In  order  to  study  the  situation  of  the 
leucocytes  sections  of  hardened  specimens  are  necessary,  but  portions  of 


60  STEUCTUIJE  OF  WHITE  THROMBI 

fresh  thrombi  teased  apart  and  treated  with  dilute  acetic  acid  are  favorable 
for  ascertaining  their  nimiber. 

In  searching  for  fibrin  in  fresh  thrombi,  it  is  important  not  to  mistake 
for  fibrin  the  threads  produced  by  compression  of  the  clumps  of  plates 
in  the  manner  already  mentioned.  If  these  flattened-out  masses  of  plates 
be  washed  with  water,  or,  better  still,  with  dilute  Lugol's  solution,  there 
may  be  produced  an  appearance  of  interlacing  and  of  parallel  threads, 
which  bear  considerable  resemblance  to  fibrin,  but  which  are  paler  and 
which  do  not  project  beyond  the  margins  of  the  clumps.  Unmistakable 
fibrin  in  the  form  of  fibrils,  however,  is  to  be  found  in  experimental 
mechanical  thrombi,  but,  so  far  as  my  observations  go,  not  in  the  earliest 
stage  of  their  formation.  I  have  found  fibrin  in  thrombi  at  the  end  of 
five  minutes;  frequently  at  the  end  of  fifteen  minutes,  and  usually  at  the 
end  of  half  an  hour.  Fibrin  is  often  found  in  so  much  larger  amount 
in  the  fresh  thrombi  than  in  sections  of  the  hardened  thrombi  that  it  is 
probable  that  it  is  formed  in  part  after  the  removal  of  the  vessel.  As  will 
be  mentioned  subsequently,  fibrin  can  be  demonstrated,  also,  in  the  hardened 
specimens,  although  not  in  the  youngest  thrombi,  I  am  not  able,  therefore, 
to  agree  with  Eberth  and  Schimmelbusch  in  denying  altogether  the  presence 
of  fibrillated  fibrin  in  experimental  thrombi  produced  by  mechanical  injury  of 
the  vessel,  although  our  observations  are  in  accord  regarding  the  youngest 
thrombi. 

I  have  dwelt  thus  at  length  upon  the  appearances  of  the  fresh  experi- 
mental thrombi  because  I  have  been  unable  to  find  any  description  of  these 
appearances.  With  the  exception  of  a  brief  allusion  by  Lubnitzky  to  sec- 
tions of  frozen  thrombi,  all  the  previous  observations  seem  to  have  been 
made  either  upon  the  mode  of  formation  of  these  thrombi  in  the  living 
circulation  or  upon  sections  of  hardened  specimens.  As  has  been  suggested 
by  Weigert,  and  as  is  apparent  from  the  foregoing  description,  a  knowledge 
of  the  gross  appearances  of  the  plate  thrombi  is  important  in  forming  a 
judgment  as  to  their  nature.  Sections  are,  of  course,  necessary  to  enable 
us  to  study  more  carefully  the  constituents  of  the  thrombi  and  particularly 
their  arrangement. 

As  already  mentioned,  I  have  made  use  chiefly  of  corrosive  sublimate 
as  a  hardening  agent,  of  paraffine  as  an  imbedding  medium,  and  of  hema- 
toxylin and  eosin  as  staining  agents."  In  sections  prepared  in  this  way 
the  plates  can  be  seen  with  a  distinctness  and  uniformity  in  shape  that 
leave  nothing  to  l)e  desired.    I  am  led  to  believe  that  most  of  the  appearances 

"  Since  the  delivery  of  this  address  I  have  also  made  use  of  Weigert's  new 
method  of  staining  fibrin  on  specimens  hardened  in  alcohol. 


STRUCTURE  OF  WHITE  THROMBI  fil 

wliitli  have  been  described  as  cluuiges  in  tlie  plates  occurring  during  the  first 
half  hour  (Lubnitzky  and  others),  are  due  to  imperfect  methods  of  harden- 
ing.   Eberth  and  Schimmelbusch  recognize  this  fact  in  their  preparations. 

Plate  thrombi  can  be  recognized  in  sections  as  well  as  in  the  fresh  state 
by  their  peculiar  translucence.  I  can  only  confirm  tlie  statments  of  Eberth 
and  Schimmeibuscli  as  to  the  composition  of  the  experimental  thrombi  in 
their  earliest  formation.  They  are  made  up  of  blood  plates.  To  the  torn 
and  partly  detached  internal  elestic  lamella  as  well  as  to  the  lacerated  media 
masses  of  plates  are  attached,  which  extend  into  the  lumen  of  the  vessel. 
Upon  sections  clumps  of  plates  often  appear  to  lie  free  in  the  lumen  sur- 
rounded by  blood,  but  subsequent  sections  show  the  connection  of  these 
clumps  with  others  or  with  parts  of  the  vascular  wall.  The  thrombus  often 
forms  a  complete  ring  around  the  torn  inner  wall  of  the  vessel.  Xot  every 
injured  part  of  the  internal  wall  of  the  vessel  is  covered  with  a  thrombus. 
One  is  often  surprised  to  find  such  parts,  even  when  severely  lacerated, 
entirely  free  from  thrombi  or  with  only  a  thin  layer  of  plates,  recognized 
with  a  high  magnifying  power.  The  mass  of  plates  composing  the. thrombus 
does  not  always  appear  uniform,  but  often,  especially  in  older  thrombi,  there 
are  lighted  and  darker  portions,  due  apparently  to  greater  density  in  the 
number  of  plates  in  some  places  than  in  others. 

An  appearance  mentioned  by  Hanau  is  of  interest,  namely,  the  pres- 
ence of  a  dark  band  around  the  margin  of  masses  or  islands  of  plates.  Simi- 
lar dense  lines  can  often  be  seen  running  irregularly  through  sections  of 
the  tliroml)us.  These  denser  bands  have  been  interpreted  as  hyaline  or  as 
fibrin.  It  is  not  easy  to  determine  their  exact  nature.  They  look  like  fibrin 
in  many  cases,  but  it  is  possible  that  they  are  produced  by  coalescence  of  the 
plates  as  the  result  of  pressure  or  traction  from  the  circulating  blood  in  a 
manner  similar  to  the  lines  which  can  be  artificially  produced  in  masses  of 
fresh  plates  by  pressure  in  the  manner  already  described.  Plates  are  not 
confined  to  the  interior  of  the  vessel,  but  when  the  internal  elastic  lamella 
and  the  media  have  been  ruptured  tliey  often  find  their  way  in  masses  into 
the  layers  of  the  torn  media  or  even  into  the  adventitia.  It  is  interesting 
to  note  the  absence  of  any  transition,  as  a  rule,  between  the  thrombus  and  the 
blood.  The  plates  are  just  as  dense  usually  at  the  margin  of  the  thrombus 
as  in  the  interior,  and  immediately  adjacent  to  the  peripheral  plates  come 
the  red  blood-corpuscles  where  the  blood  was  still  circulating  before  the  ves- 
sel was  removed. 

Leucocytes  are  not  generally  present  in  large  number  in  thrombi  during 
the  first  five  minutes  of  their  formation.  If  serial  sections  be  examined, 
here  and  there  clumps  of  white  corpuscles  can  be  found  even  at  this  early 
stage.    There  are  often  more  white  corpuscles  mingled  with  the  plate  masses 


62  STRUCTURE  OF  WHITE  THROMBI 

in  the  coats  of  the  vessel  than  in  the  thromi)us  proper.  Leucocytes,  scanty 
at  first,  continue  to  accumulate  in  larger  and  larger  number,  until  they 
form  a  prominent  part  of  the  thrombus.  I  have  found  them  in  great  abun- 
dance at  the  end  of  half  an  hour,  although  sometimes  at  this  period  their 
number  is  small.  The  leucocytes  are  generally  arranged  in  clumps  between 
masses  of  plates,  although  some  are  usually  scattered  in  among  the  plates.  It 
is  probable  that  the  clumps  of  leucocytes  are  deposited  in  that  form  directly 
from  the  circulating  blood.  There  is  reason  to  believe  that  the  leucocytes 
may  also  wander  into  the  thrombus,  for  in  sublimate  specimens  elongated 
nuclei,  such  as  are  seen  in  undoubtedly  wandering  white  corpuscles  in  the 
wall  of  the  vessel,  can  also  be  occasionally  detected  in  the  masses  of  plates. 
Moreover,  the  number  of  leucocytes  within  these  masses  increases  with  time. 
In  successfully  prepared  sections  the  protoplasm  can  be  seen  around  the 
nuclei  of  the  white  corpuscles,  so  that  I  do  not  agree  with  Lubnitzky  that 
this  has  become  merged  with  the  plates.  Sometimes  the  leucocytes  are  sur- 
rounded with  a  clear  zone  as  if  they  lay  in  little  spaces  within  the  mass  of 
plates,  but  this  appearance  is  probably  due  to  the  action  of  the  hardening 
fluid.  Both  uninuclear  and  multinuclear  white  corpuscles  are  present,  but 
the  latter  predominate,  and  in  the  later  stages  many  of  the  nuclei  often 
appear  much  broken  up. 

Although  I  have  not  seen  any  appearances  which  indicate  that  the  white 
corpuscles  disintegrate  into  granules,  still  non-nucleated  white  corpuscles 
can  sometimes  be  detected,  so  that  a  necrosis  or  death  of  these  corpuscles 
may  take  place  within  the  thrombus.  This  does  not  seem,  however,  to  be 
a  common  or  extensive  process. 

As  has  already  been  stated,  fibrillated  fibrin  is  present  in  experimental 
throml)i  produced  by  mechanical  injury  of  the  vessel.  It  is  not,  however, 
found  in  the  youngest  thrombi,  and  the  date  of  its  appearance  varies  in 
different  cases.  I  have  found  it  in  hardened  specimens  at  the  end  of  five 
minutes,  but  this  is  exceptional.  It  is  not  uncommon  to  find  it  at  the  end 
of  fifteen  minutes.  I  exhibit  under  the  microscope  sections  of  a  tlirombus 
of  one-half  hour's  duration,  in  which  there  is  a  considerable  amount  of  dis- 
tinct fibrillated  fibrin.  The  amount  of  fibrin  increases  witli  the  age  of  the 
thrombus,  and  in  thrombi  of  twenty-four  hours'  duration  fibrin  makes  up 
usually  a  large  part  of  the  thrombus. 

The  fibrin  appears  in  islands  and  bands  between  the  masses  of  plates,  and 
often  extends  in  coarse  fibres  into  tlie  surrounding  blood.  The  net-work  is 
usually  coarse,  but  fine  threads  are  also  present.  After  a  time  the  clumps  of 
white  and  of  red  corpuscles  included  in  the  thrombus  are  pervaded  by  a  net- 
work of  fibrin,  whereas,  this  is  absent  in  the  dense  clumps  of  plate-s.  I  have 
the  impression  that  there  is,  in  general,  a  relation  between  the  number  of 


STRUCTURE  OF  WHITE  THROMBI  63 

leucocytes  and  the  amount  of  fibrin,  althougli  tlie  former  appear  in  con- 
siderable quantity  before  tlie  latter. 

Inasmuch  as  in  older  thrombi  (twenty-four  to  forty-eight  hours)  fibrin 
and  leucocytes  compose  a  large  part  of  the  thrombus,  whereas,  at  its  incep- 
tion the  thrombus  is  made  up  almost  entirely  of  blood  plates,  one  is  tempted 
to  believe  that  the  plates  may  ])e  transformed  into  fibrin,  but  of  this  trans- 
formation I  can  bring  no  positive  proof.  The  plate-masses,  after  a  time, 
lose  their  regular  granular  appearance  and  appear  darker  in  color  and  more 
homogeneous,  but  typical  plates  may  be  found  in  large  number  in  thrombi 
forty-eight  hours  old. 

It  is  apparent  from  the  foregoing  description,  that  experimental  thrombi 
acquire  witli  time  all  of  the  characteristics  of  human  thrombi.  The  sus- 
picion which  has  been  raised  that  they  represent  a  distinct  class  of  thrombi, 
from  the  study  of  which  we  can  draw  no  conclusion  as  to  the  formation  of 
human  thrombi,  is  unjustifiable.  It  is  another  question  whether  we  are  to 
suppose  that  all  human  white  thrombi  are  formed  in  the  manner  described. 
Although  I  have  not  succeeded  in  producing  permanent  leucocytic  thrombi 
experimentally,  still  there  is  every  reason  to  believe  that  some  human 
thrombi  are  composed  from  the  beginning  essentially  of  leucocytes.  In 
observations  which  I  have  made  recently  for  another  purpose,  of  the  living 
circulation  in  the  mesentery  of  dogs,  I  have  observed  the  formation  of 
small  parietal  thrombi  composed  of  white  corpuscles,  but  these  have  in- 
variably been  washed  away  after  a  short  time. 

We  may,  it  seems  to  me,  think  of  the  mode  of  formation  of  the  experimental 
thrombi,  which  we  have  studied,  and  doubtless  also  of  many  human  thrombi 
as  follows :  Given  suitable  conditions,  such  as  alteration  of  the  vessel  wall, 
slowing  and  irregularity  of  the  circulation,  the  first  constituents  of  the 
thrombus  to  accumulate  are  tlie  blood  plates.  But  although  the  plates 
collect  at  first  in  larger  nimiber  and  more  rapidly,  the  leucocytes  do  not  long 
remain  absent,  and  in  the  course  of  time  they  are  present  in  such  quantity 
that  they  must  be  considered  an  essental  constituent  of  the  completed 
thrombus.  At  first  the  conditions  for  the  coagulation  of  fibrin  are  not 
present,  but  with  the  increasing  accumulation  of  leucocytes  these  conditions 
appear  and  fibrillated  fil)rin  is  deposited.  It  is  in  harmony  with  tlie  current 
ideas  concerning  the  cause  of  the  coagulation  of  fibrin,  to  suppose  that  at 
first  the  fibrin  ferment  is  absent,  and  that  this  is  subsequently  furnished 
by  the  leucocytes.  The  absence  of  fibrin  in  the  early  thrombi  composed 
wholly  of  plates,  is  an  argument  additional  to  the  evidence  brought  forward 
by  Lowit  and  others,  that  the  plates  do  not  furnish  tlie  fibrin  ferment.  It  is 
apparently  only  after  the  leucocytes  have  been  included  for  a  time  in  the 
thrombus  tliat  they  die  or  undergo  some  alteration  in  their  constitution 


G4  STRUCTUEE  OF  WHITE  THROMBI 

whicli  leads  to  the  formation  of  the  fibrin  ferment.  The  final  result  is  a  plug 
composed  of  plates,  leucocytes,  and  fibrin,  and  included  red  blood-corpuscles. 

It  seems  to  me  an  error  to  ba5c  our  conception  of  the  nature  of  a  thrombus 
exclusively  upon  the  constitution  of  tlie  tlirombus  in  its  inception.  While 
admitting  that  the  tlirombus  is  at  first  composed  wholly  of  blood  plates,  we 
do  not,  as  a  matter  of  fact,  meet  with  huniaji  thrombi  in  this  early  stage,  or 
at  least,  only  under  exceptional  circumstances.  Our  ideas  as  to  the  constitu- 
tion of  thrombi  are  based  upon  the  examinations  of  the  completed  plugs 
which  contain  fibrin  and  leucocytes  as  well  as  plates.  The  study  of  the 
experimental  tlirombi  enables  us  to  form  a  clearer  conception  of  the  mode 
of  formation  of  the  thrombus,  but  does  not  necessitate  any  radical  change  in 
our  ideas  as  to  what  constitutes  a  thrombus. 

The  question  as  to  whether  a  thrombus  is  a  coagulum  or  not,  is,  of  course, 
open  to  discussion  only  regarding  the  plate  thrombi  in  their  earliest  forma- 
tion. W^hether  or  not  we  are  to  regard  the  plat-e  throml)i  before  fibrin  has 
made  its  appearance  as  coagula,  is  a  question  which  is  not  likely  to  be  settled 
until  we  acquire  more  definite  information  as  to  the  origin  and  nature  of 
the  blood  plates.  There  is  nothing  in  the  gross  appearances  of  these  plate 
thrombi  which  would  prevent  us  from  considering  them  as  soft,  gelatinous 
coagula.  Wooldridge,  Lowit,  and  others  believe  that  the  plates  are  allied  to 
fibrin  but  are  not  identical  with  it.  I  purposely  avoid  entering  into  any 
discussion  here  as  to  their  existence  in  the  nortnal  circulation,  for  tliis  is  a 
point  which  must  still  be  regarded  as  sub  judice,  and  which  is  not  likely  to 
be  settled  by  the  experimental  study  of  thromlii. 

The  attempt  of  Eberth  and  Schinnnelbusch  to  draw  a  sharp  distinction 
between  tlirombi  formed  by  conglutination  and  thrombi  formed  by  coagula- 
tion, seems  to  me  unwarranted.  In  the  first  place  the  process  which  they 
designate  as  conglutination  may  be,  so  far  as  we  at  present  know,  a  form  of 
coagulation.  In  the  second  place,  whatever  we  may  think  as  to  the  nature  of 
the  process  of  conglutination,  the  preceding  investigations  have  demon- 
strated tlie  transformation  of  conglutionation  thrombi  into  undoubted  coagu- 
lation thrombi. 

As  regards  the  relation  between  changes  in  the  walls  of  the  vessels  and 
thrombosis,  I  have  reached  the  same  conclusion  as  tliat  expressed  by  von 
Recklinghausen,  Eberth  and  Schimmellmsch,  and  others,  that  Cohnheim's 
views  on  this  point  were  too  exclusive.  It  is  possible  to  produce  experi- 
mentally severe  injury  of  the  internal  coats  of  bloodvessels  without  any 
resulting  thrombus.  Among  many  positive  results  I  have  also  in  my  notes 
the  records  of  not  a  few  negative  results  which  have  followed  injury  of  the 
walls  of  the  vessels  by  caustics,  by  forcible  application  of  rough  clamps,  by 
scraping  the  interior  of  tlie  vessel,  etc.    As  is  urged  by  these  writers  as  well 


STRUCTURE  OF  WHITE  THROMBI  65 

as  by  Weigert  and  others,  slowing  of  the  circulation  and  irregularities  of 
the  circulation  produced  by  abnormalities  in  the  lumen  of  the  bloodvessels, 
are  factors  no  less  important  in  tlie  production  of  thrombi  than  alterations 
in  the  vessel  walls. 

There  is  much  which  speaks  for  the  correctness  of  the  view  advocated  by 
Kohler,  Hanau,  and  others,  that  some  thrombi  are  caused  by  fermentative 
changes  in  the  blood.  Cases  such  as  the  one  already  mentioned,  of  extensive 
thrombosis  of  a  large  number  of  the  bloodvessels  tliroughout  the  body,  are 
most  naturally  interpreted  as  examples  of  fermentation  thrombosis. 


HEMOREHAGIC  INFARCTION' 

Of  the  various  aspects  of  the  subject  of  hemorrhagic  infarction,  I  have 
selected  for  my  contribution  to  this  discussion  that  which  relates  to  the 
mechanism  by  which  the  hemorrhage  is  produced  in  the  infarction. 

Together  with  Dr.  F.  P.  Mall,  Fellow  in  Pathology  of  the  Johns  Hopkins 
University,  I  have  undertaken  some  experiments  in  order,  if  possible,  to  be 
able  to  form  an  independent  and  positive  judgment  as  to  some  of  the 
unsettled  questions  which  pertain  to  hemorrhagic  infarction.  It  seemed  to 
me  hardly  worth  while  to  present  to  an  audience  of  this  character,  merely  a 
critical  review  of  the  many  opinions  which  have  been  and  are  held  as  to  the 
mode  of  production  of  hemorrhagic  infarction. 

Before  communicating  the  results  of  our  experiments,  I  will  call  your 
attention  to  the  history  of  opinion  concerning  the  nature  of  hemorrhagic 
infarction,  in  order  that  we  may  understand  the  present  aspect  of  the  subject. 

The  first  clear  anatomical  description  of  hemorrhagic  infarction  was  given 
by  Laennec,'  in  1819,  under  the  name  of  pulmonary  apoplexy.  He  seems 
to  have  regarded  the  condition  as  analogous  to  cerebral  hemorrhage,  but  he 
expressed  no  positive  opinion  as  to  the  causation. 

After  Laennec,  Bouillaud,"  Cruveilliier,*  and  several  other  noted  the 
presence  of  coagula  in  the  arteries  and  veins  adjacent  to  hemorrhagic  infarc- 
tions, but,  in  accordance  with  the  pathological  views  of  that  time,  they 
interpreted  these  coagula  as  evidence  of  phlebitis.  This  gave  origin  to  the 
doctrine,  advocated  especially  by  Bochdalek,"  that  hemorrhagic  infarctions 
are  inflammatory  in  their  nature  and  due  to  a  primary  capillary  phlebitis. 

Rokitansky,  in  the  first  edition  of  his  "  Pathological  Anatomy,"  also 
attributed  the  origin  of  hemorrhagic  infarction  to  capillary  thrombosis,  but, 
in  conformity  with  the  humoral  pathology  of  the  Vienna  school,  he  regarded 
this  thrombosis  of  the  capillaries  as  referable  not  to  inflammation  but  to  a 
change  in  the  constitution  of  the  blood.' 

'  Delivered  before  the  Association  of  American  Physicians,  Army  Medical 
Museum,  Washington,  D.   C,  June  2,   1887. 

Tr.  Ass.   Am.  Physicians,   Phila.,    1887,    II,   121-132. 

'Laennec:     De  I'Auscultation  Mediate,  t.    II,  p.  41.     Paris,   1819. 

•Bouillaud:     Arch.  g6n.,  1826.  t.  XII.  p.  392. 

*  Cruveilhier:     Anat.   Path.,   livr.    III. 

'Bochdalek:     Prager  Vierteljahrsschrift.   1846,  Bd.   IX. 

•Rokitansky:  Handb.  d.  Path.  Anat.,  Bd.  II,  p.  680  et  seq.,  Wien,  1844.  Bd. 
I,  p.  243,  Wien,  1846. 

66 


HEMORRHAGIC  IXFARCTIOX  67 

Virchow/  by  his  memorable  articles  on  thrombosis  and  embolism,  pub- 
lished between  1846  and  1856,  overthrew  phlebitis  from  the  dominant  role 
in  pathology  which  it  had  assumed  through  the  teachings  of  Cniveilhier,  and 
he  introduced  and  established  upon  a  firm  basis  the  doctrine  of  embolism. 
He  did  not,  however,  reach  any  positive  conclusion  as  to  the  nature  and 
mode  of  production  of  hemorrhagic  infarction.  In  his  earlier  writings  he 
was  inclined  to  regard  the  ante-mortem  coagula  occluding  arteries  leading 
to  pulmonary  hemorrhagic  infarctions  as  secondary  to  the  infarction  and 
not  concerned  in  its  causation.  This  view  was  based  chiefly  upon  his  fail- 
ure to  produce  hemorrhagic  infarction  experimentally  by  injecting  into  the 
blood  emboli  which  lodged  in  branches  of  the  pulmonary  artery. 

Virchow  subsequently  became  doubtful  as  to  the  secondary  nature  of  the 
plugs  occluding  the  arteries  leading  to  infarctions  by  the  observation  of 
cases  of  hemorrhagic  infarction  of  the  intestine  in  connection  with  embolism 
of  the  superior  mesenteric  artery.  In  an  article  published  in  1852,  reporting 
a  case  of  embolism  of  the  superior  mesenteric  artery,  he  suggested  as  pos- 
sibilities most  of  the  explanations  which,  have  since  been  advanced  to  account 
for  the  apparently  paradoxical  phenomenon  that  the  occlusion  of  an  artery 
is  followed  by  hyperasmia  and  hemorrhage  in  the  region  supplied  by  this 
artery.  He  laid  especial  emphasis  upon  changes  in  the  vascular  wall  as  the 
result  of  prolonged  ischsemia  and  upon  increased  pressure  in  the  collateral 
vessels.  He  also  dwelt  upon  irregularities  in  the  circulation  leading  to 
stasis  in  some  of  the  open  vessels  of  the  district  whose  artery  is  occluded. 
In  another  connection,  when  treating  of  ischaemia,  Virchow  calls  attention 
to  the  possibility  of  a  regurgitant  flow  of  blood  from  the  veins  when  the  cor- 
responding arteries  are  obstructed.*  Virchow's  chief  motive  in  adducing 
changes  in  the  walls  of  the  bloodvessels  as  an  essential  factor  in  the  causation 
of  hemorrhagic  infarction  is  the  apparent  impossibility  of  explaining  the 
occurrence  of  the  hemorrhage  on  purely  mechanical  grounds. 

Notwithstanding  the  cautious  manner  in  which  Virchow  expressed  him- 
self upon  the  relation  between  embolism  and  hemorrhagic  infarction,  it  has 
been  accepted  by  nearly  all  subsequent  writers  that  obstruction  of  an  artery 
may  lead  to  hemorrhagic  infarction  in  the  region  supplied  by  that  arter}', 
provided  suitable  conditions  in  the  collateral  circulation  exist 

'Virchow:     Gesammelte    Abhandlungen,   1856. 

'Virchow:  Handb.  d.  spec.  Path.  u.  Ther.,  Bd.  I,  p.  127.  Erlangen,  1857. 
It  is  true,  as  pointed  out  by  Mogling  (Ziegler  u.  Nauwerck's  Beitrage  z. 
Path.  Anat.,  Bd.  I,  p.  145.  Jena,  1886),  that  Virchow  does  not  apply  this  factor 
to  the  explanation  of  the  production  of  hemorrhagic  infarction,  but  it  is 
apparent  that  the  reasoning  which  he  employs  to  explain  venous  regurgitation 
in  partial  anaemia  applies  to  the  condition  present  when  hemorrhagic  infarc- 
tion follows  arterial  obstruction. 


68  TTEMORRHAGIC  INFARCTIOX 

The  first  to  apply  directly  to  the  explanation  of  hemorrhagic  infarction 
a  regurgitant  flow  of  blood  through  the  veins  of  the  district  the  artery  of 
which  is  obstructed,  was  B.  Cohn,"  in  1856.  This  view,  however,  he  sub- 
sequently abandoned  "  on  the  ground  of  experiments,  which,  nearly  twenty 
years  afterward,  Avere  repeated  by  Litteu.  Cohn  found  that  not  only  do 
hypera?niia  and  hemorrhagic  infarction  occur  when  both  artery  and  vein  of 
a  part  are  tied,  but  the  hypera^mia  is  more  intense  than  when  the  artery 
alone  is  ligated.  Moreover,  when  all  connection  of  a  part  with  the  circu- 
lation, except  through  the  vein,  is  cut  off,  no  hemorrhage  follows.  Cohn, 
in  his  later  work,  regarded  most  hemorrahgic  infarctions  as  referable  essen- 
tially to  capillary  obstruction,  and,  as  a  rule,  not  capable  of  production 
merely  by  occlusion  of  a  main  artery.  He  did  not  separate  infarction, 
particularly  renal  and  pulmonary  infarctions,  clearly  from  inflammation, 
an  error  into  which  Panum  also  fell." 

Regurgitation  of  venous  blood  was  accepted  by  Beckmann "  as  the 
explanation  of  hemorrhagic  infarction  of  the  intestine  following  embolism 
of  the  superior  mesenteric  artery.  He  refers  to  the  statments  upon  this 
point  of  Virehow  and  of  Cohn,  and  says  that  it  is  difficult  to  conceive  that 
the  blood  which  produces  the  uniform  hemorrhagic  extravasation  over 
nearly  the  whole  extent  of  the  small  intestine  can  come  from  the  distant 
arterial  anastomoses.  To  Beckmann  belongs  the  credit  of  pointing  out 
that  most  of  the  infarctions  of  the  kidney  are  from  the  beginning  pale  and 
unattended  with  much  hemorrhage." 

Blessig,"  in  an  experimental  work  on  changes  in  the  kidney  following 
ligation  of  the  renal  artery,  performed  under  Virchow's  direction,  came 
to  the  conclusion  that  obstruction  of  an  artery  is  followed  by  hemorrhagic 
infarction  only  when  the  corresponding  vein  is  likewise  occluded.  It  is 
noteworthy  that  he  observed  hemorrhagic  extravasation  in  the  kidney  after 
ligation  of  both  renal  artery  and  vein. 

An  epoch  in  the  history  of  our  subjects  is  marked  by  the  publication, 
in  1872,  of  Cohnheinrs  "  Investigations  Concerning  the  Embolic  Pro- 
cesses."" Cohnheim  studied  microscopically,  in  the  tongue  of  curarized 
frogs,  the  process  of  formation  of  hemorrhagic  infarctions  produced  by 
artificial  emboli  which,  after  introduction  into  the  aorta,  lodged  in  branches 

°  B.  Cohn:     De  Embolia  ejusque  sequelis.     Diss.,  1856. 

"B.  Cohn:    Klinik  d.  embolischen  gefasskrankh.     Berlin,  1860. 

"Panum:     Virchows   Archiv,    1862,   Bd.    25,   p.   433. 

"Beckmann:    Virchow's  Archiv,  1858,  Bd.  13,  p.  504. 

"Ibid.,   op.   cit.,   1861,   Bd.   20,   p.   219. 

"Blessig:     Virchow's   Archiv,  1859,  Bd.  16,  p.   120. 

"Cohnheim:     Untersuchungen   iiber  die  embolischen   Procease.     Berlin,  1872. 


HEMORRHAGIC  INFARCTION  69 

of  the  lingual  arteries.  He  reached  the  conclusions  that  the  blood  which 
produces  the  infarction  is  derived  by  regurgitant  flow  from  the  veins,  that 
the  hemorrhage  occurs  by  diapedesis,  and  that  the  diapedesis  is  the  result 
of  some  molecular  alteration  in  the  vascular  walls  deprived  of  their  normal 
circulation.  The  hemorrhage  occurs  some  time  after  the  embolic  occlusion 
of  the  artery.  In  this  article  Cohnheim  also  considers  the  peculiarities 
of  the  circulation  in  the  organs  which  are  most  frequently  the  seat  of 
infarction,  and  thereby  laid  down  his  doctrine  of  terminal  arteries  (endar- 
terien) — that  is,  arteries  the  branches  of  which  do  not  anastomose  with 
each  other. 

Although  Cohnheim  made  no  attempt  to  reconcile  his  views  with  the 
opposing  conclusions  reached  experimentally  by  Cohn  and  Blessig,  never- 
theless the  authority  of  his  name,  the  clear  and  admirable  presentation 
of  his  experiments,  the  inherent  reasonableness  of  liis  views,  and  the  fact 
that  they  were  deduced  from  actual  observation  under  the  microscope, 
combined  to  win  general  acceptance  for  Cohnheim's  explanation  of  hemorr- 
hagic infarction. 

This  explanation,  however,  did  not  long  remain  unchallenged,  for  in  the 
year  following  Cohnheim^s  publication,  Zielonko,"  who  worked  under  von 
Recklinghausen's  direction,  reached  a  different  conclusion  as  to  the  causation 
of  hemorrhages  following  arterial  obstruction.  Zielouko's  observations  were 
upon  the  web  of  the  frog's  foot.  The  main  points  in  Zielonko's  conclusions 
which  interest  us,  are  that  the  blood  which  produces  the  hemorrhages  after 
obstruction  of  an  artery,  comes  from  the  collateral  vessels  and  not  by  a 
reflux  from  the  veins,  and  that  the  hemorrhage  is  at  least  quite  as  much 
the  result  of  stasis  in  the  capillaries,  and  consequently  increased  pressure, 
as  of  changes  in  the  vascular  walls.  A  regurgitant  flow  of  blood  in  the 
veins  may  occur,  but  this  does  not  extend  so  far  back  as  the  capillaries,  and 
has  no  share  in  the  formation  of  the  stases. 

Similar  results  were  obtained  by  Kossuchin,'^  who  worked  under  Afanas- 
siew's  direction,  and  published  his  article  in  1876.  He  repeated  Cohn- 
heim's experiments  upon  the  frog's  tongue.  He  was  unable  to  observe 
reflux  of  blood  from  the  veins  into  the  capillaries  belonging  to  the  obstructed 
arteries,  and  he  attributes  the  hypcra?mia  of  the  district  whose  artery  is 
occluded  chiefly  to  collateral  fluxion.  Hemorrhages  occur  by  diapedesis 
only  in  the  periphery  of  the  embolized  area  and  in  the  surrounding  zone 
of  collateral  hyperaemia ;  at  a  later  period,  when  necrosis  sets  in,  liemor- 
rhages  occur  throughout  the  embolized  area,  and  are  due  probably  to  necrosis 

'*Zielonko:     Virchow's  Archiv,   1873,  Bd.  57,  p.  436. 
"Kossuchin:    Virchow's  Archiv,  1876.  Bd.  67,  p.  449. 


70  HEMOERHAGIC  INFARCTION 

of  the  vessel  walls.  The  early  hemorrhages  occur  especially  from  capillaries 
in  the  condition  of  stasis,  or  adjacent  to  such  stases,  and  are  probably 
referable  to  increased  blood  pressure. 

The  careful  observations  of  Zielonko  and  Kossuchin  seem  to  have  had 
little  or  no  influence  in  preventing  the  general  acceptance  of  Cohnheim's 
teacliings.  On  the  other  hand,  the  more  pointed  attack  of  Litten  "  upon 
Cohnheim's  doctrine  has  had  greater  influence  upon  the  current  views  con- 
cerning the  production  of  hemorrhagic  infarction.  Litten  concludes  that 
the  hypcrtemia  and  hemorrhage  which  follow  ligation  of  the  renal  artery 
cannot  be  due  to  a  regurgitant  flow  of  blood  in  the  renal  vein,  because 
the  same  or  an  even  greater  hyperemia  follows  when  both  artery  and 
vein  are  ligated,  and  no  such  result  occurs  if  all  connection  of  the  kidney 
with  the  circulation,  save  through  the  renal  vein,  be  cut  off.  The  only 
possible  source  for  the  increased  supply  of  blood  is  the  collateral  circulation. 
Similar  experiments  were  made  upon  the  lung  and  the  spleen.  Litten's 
experiments  upon  this  point  are  essentially  a  repetition  of  those  performed 
twenty  years  previously,  with  the  same  results,  by  Cohn.  Of  Cohn's  mani- 
fold experiments  upon  the  kidney,  spleen,  and  intestine,  to  disprove  the 
agency  of  regurgitation  of  venous  blood  in  the  causation  of  hemorrhagic 
infarction,  Litten  seems  to  have  been  ignorant,  for  they  are  not  mentioned 
in  his  article.  Litten  also  denies  the  efficacy  of  a  second  factor,  which  Vir- 
chow  and  C'ohnhcim  had  adduced  to  explain  the  occurrence  of  hemorrhagic 
infarction,  namely,  changes  in  the  walls  of  the  vessels  produced  by  pro- 
longed ischaemia.  This  denial  is  based  first  upon  the  fact  that  hyperaemia 
and  diapedesis  begin  in  a  very  short  time  after  ligation  of  the  renal 
artery,  and,  secondly,  upon  the  absence  of  any  hemorrhage  which  can  pos- 
sibly be  attributed  to  changes  in  the  vascular  walls,  in  cases  when  the  cir- 
culation has  been  reestablished  in  the  kidney  of  the  rabbit  after  its  cessation 
for  three  or  four  hours.  The  same  conclusions  had  been  previously  drawn 
by  Kossuchin  from  experiments  of  the  same  nature  made  upon  frogs. 

Von  Recklinghausen,"  in  an  admirable  chapter  upon  thrombosis  and  embol- 
ism, has  called  attention  to  a  new  factor  in  the  causation  of  hemorrhagic 
infarction,  namely,  hyaline  thrombosis  of  the  capillaries.  He  has  observed 
hyaline  thrombi  in  the  capillaries  in  all  hemorrhagic  infarctions  of  the 
lung  examined  in  recent  years,  as  well  as  in  hemorrhagic  infarctions  of  the 
spleen.     The  obstruction   to  the  circulation   produced   by  these   thrombi 

"Litten:    Zeitschrift  f.  klin.  Med.,  Bd.  1,  p.  131. 

"Von  Recklinghausen:  Handb.  d.  Allg.  Path.  d.  Kreislaufs  u.  d.  Ernahrung, 
p.  160.    Stuttgart,  1883. 


HEMORRHAGIC  INFARCTIOX  71 

causes,  he  believes,  a  rise  in  pressure  and  hemorrhage.  The  blood  enters 
from  the  collateral  channels. 

This  review  of  the  history  of  opinion  concerning  hemorrhagic  infarction 
makes  it  evident  that  there  is  still  much  to  explain  in  the  causation  of  this 
condition,  and  that  there  is  abundant  opportunity  for  further  experimental 
work. 

The  experiments  of  Dr.  Mall  and  myself  relate  to  hemorrhagic  infarction 
of  the  intestine,  and  were  performed  almost  wholly  upon  dogs.  The  intes- 
tine offers  many  advantages  for  the  experimental  study  of  hemorrhagic 
infarction.  It  is  easy  to  produce  infarction  in  this  situation,  whereas  it  is 
difficult  to  produce  hemorrhagic  infarction  of  the  lung  artificially.  The 
circulation  of  blood  in  the  spleen  is  of  so  peculiar  a  nature  that  tbis  organ 
is  less  adapted  to  our  purpose  than  the  intestine.  Infarction  of  the  kidney 
in  man  is  usually  a  white  infarction,  with  only  a  margin  of  extravasated 
blood.  As  is  well  known,  occlusion  of  the  superior  mesenteric  artery  in 
man  is  followed  by  hemorrhagic  infarction  extending  throughout  nearly 
the  whole  length  of  the  small  intestine,  and  even  into  the  upper  part  of 
the  large  intestine. 

In  the  mesentery  the  condition  of  the  circulation  can  be  modified  in 
many  ways.  The  branches  of  the  superior  mesenteric  artery  anastomose 
freely,  forming  in  the  dog  only  one  row  of  arches,  from  the  summits  of 
which  branches  are  given  off  which  enter  the  walls  of  the  intestine.  It  is 
possible  to  convert  any  one  of  these  main  arteries  into  a  terminal  artery. 
The  collateral  circulation  can  be  limited  to  any  extent  desired.  The  intes- 
tine offers  the  advantage  that  it  is  easy  to  look  over  its  M^hole  extent  and 
determine  the  exact  situation  and  character  of  an  infarction. 

Of  importance  is  the  high  pressure  in  the  veins  leading  from  the  intestine. 
The  blood  pressure  in  the  mesenteric  and  portal  veins  is  higher  than  in 
any  portion  of  the  venous  system.  We  have  found  the  pressure  in  the 
superior  mesenteric  vein  equal  to  from  30  to  50  mm.  of  mercury.  If  regTirgi- 
tation  of  blood  from  the  veins  is  a  factor  in  the  production  of  hemorrhagic 
infarction,  it  should  be  apparent  here. 

If  the  superior  mesenteric  artery  be  ligated  near  its  origin,  there  follows 
an  intense  hemorrhagic  infarction  which  begins  about  five  or  six  hours 
after  the  ligation,  and  increases  in  intensity  until  it  reaches  its  maximum 
about  seven  or  eight  hours  after  the  obstruction  was  produced.  If  the  ani- 
mal be  now  killed,  it  is  found  that  the  hemorrhagic  infarction  begins 
abruptly  with  a  sharp  line  of  demarcation  in  the  lower  part  of  the  duodenum. 
It  reaches  its  greatest  intensity  within  an  inch  or  two  of  its  beginning,  and 
extends  throughout  the  whole  length  of  the  small  intestine  into  the  colon, 
where  it  gradually  diminishes  in  intensity,  but  still  ends  somewhat  abruptly. 


72  HEMORRHAGIC  IXFARCTIOX 

The  hyperEemia  and  hemorrhage  begin  in  the  mucous  membrane,  and  are 
more  intense  there  than  in  any  of  the  other  coats.  The  mucous  membrane 
is  of  a  dark  red,  almost  black  color.  The  submucous  coat  also  becomes  infil- 
trated with  blood,  but  the  muscular  coat  is  much  prone  to  hemorrhage.  The 
lumen  of  the  intestine  contains  much  dark  blood  mixed  with  mucus.  Upon 
microscopical  examination  the  capillaries  and  veins,  particularly  of  the 
mucosa,  are  engorged  with  blood,  and  there  is  extravasation  of  blood  into 
the  tissues. 

The  first  point  which  we  wished  to  settle  is  the  source  of  the  blood  which 
causes  the  hyperamiia  and  hemorrhage  after  ligation  of  the  superior  mes- 
enteric artery.  This  blood  must  come  either  from  the  collateral  arterial 
and  capillary  anastomoses  or  by  a  regurgitant  flow  from  the  veins.  The 
collateral  anastomosis  above  is  with  the  pancreatico-duodenal  artery,  that 
below  with  the  inferior  mesenteric  artery. 

In  order  to  determine  whether  a  regurgitant  flow  of  blood  from  the  veins 
is  the  source,  we  ligated  the  superior  mesenteric  vein  coincidently  with 
ligation  of  the  artery,  and  found  that  the  infarction,  instead  of  diminishing 
in  intensity,  became  more  marked,  and  was  established  at  an  earlier  period. 
The  same  results  were  obtained  by  ligation  of  the  superior  and  inferior 
mesenteric  veins,  and  by  ligation  of  the  portal  vein  at  the  same  time,  with 
that  of  the  superior  mesenteric  artery.  It  seemed,  therefore,  certain  that 
a  regurgitant  flow  of  blood  from  the  veins  is  not  the  cause  of  the  infarction. 
In  order  to  remove  all  doubt,  we  isolated  the  intestine  from  all  its  connec- 
tions with  the  circulation,  except  through  the  superior  mesenteric  vein. 
And,  although  we  convinced  ourselves  that  no  thrombosis  had  occurred  in 
this  vein,  there  resulted  no  hypercrmia  or  hemorrhage  in  the  intestine.  We 
have  repeated  this  experiment  with  a  loop  of  intestine,  and  always  with 
the  same  result,  death  of  the  part,  but  no  hemorrhagic  infarction.  It  will 
be  remembered  that  the  pressure  in  the  veins  is  high,  so  that  if  a  regurgitant 
flow  of  blood  in  tlie  veins  is  a  factor,  it  should  certainly  be  manifest  here. 

In  order  to  determine  to  what  extent  the  collateral  circulation  may  be 
cut  off',  and  still  hemorrhagic  infarction  follow,  we  ligated  the  superior 
mesenteric  artery,  coeliac  axis,  and  portal  vein,  and  in  another  series  of 
experiments,  in  addition  to  the  ligation  of  these  vessels,  we  ligated  the 
duodenum  and  the  ileum,  not  far  from  the  ilcocoecal  valve.  Under  those 
circumstances  the  collateral  anastomosis  must  be  slight,  and  yet  hemorrhagic 
infarction  occurred.  The  collateral  anastomoses,  however,  without  being 
completely  cut  off,  may  be  so  reduced  that  they  do  not  suffice  for  the  pro- 
duction of  hemorrhagic  infarction.  Thus,  if  the  vessels  (including  the 
subintestinal  plexus)  and  the  intestine  be  so  tied  that  the  blood  can  enter 
only  through  the  vessels  in  the  intestinal  wail  at  the  lower  end  of  the  loop, 


HEMORRHAGIC  INFARCTION  73 

it  iri  found,  if  the  loop  be  a  long  one,  tliat  hemorrhage  makes  its  appearance 
only  in  the  lower  end,  and,  after  extending  a  short  distance,  ceases,  to  be 
replaced  first  by  patches  of  hemorrhages,  and  then  by  simple  anaemic  necrosis. 

We  wished  to  determine  another  point,  of  some  theoretical  interest  at 
least,  namely,  whether  the  blood  which  produces  hemorrhagic  infarction 
must  enter  from  the  collateral  channels.  For  this  purpose  we  ligated  all 
of  the  vascular  communications  of  the  intestine,  with  the  exception  of  the 
main  artery  and  the  main  vein,  and  then  tied  the  intestine  above  and  below, 
so  that  the  included  intestine  was  supplied  only  by  the  main  arter}',  and  the 
blood  returned  by  the  main  vein.  Under  these  circumstances  no  infarction 
results.  We  then  placed  a  rubber  clamp  around  the  artery,  and  gradually 
tightened  it,  so  that  the  blood  circulated  with  less  and  less  force.  We  carried 
the  compression  so  far  that  the  pulsations  disappeared  in  the  branches  of 
the  artery,  although  the  blood  still  continued  to  flow,  as  was  demonstrated 
by  cutting  one  of  the  branches.  By  thus  obstructing  the  circulation  in  the 
main  artery,  while  all  collateral  anastomoses  were  cut  off,  we  succeeded  in 
producing  hemorrhagic  infarction  of  the  included  part  of  the  intestine. 
This  experiment  sheds  some  light  upon  the  condition  of  the  circulation  dur- 
ing the  production  of  hemorrhagic  infarction. 

We  wished  to  measure  the  blood  pressure  in  a  part  in  which  hemorrhagic 
infarction  is  taking  place.  To  accomplish  this  we  inserted  a  canula,  con- 
nected with  a  mercury  manometer,  into  a  branch  of  the  superior  mesenteric 
artery.  Immediately  after  ligation  of  the  superior  mesenteric  artery,  the 
pressure  fell  from  130  mm.  to  about  30  mm.,  and  remained  at  about  this 
point  during  the  whole  time  the  infarction  was  taking  place.  We  may,  there- 
fore, conclude  that  the  arterial  tension  in  a  part  where  hemorrhagic  infarc- 
tion is  occurring,  is  very  low.  As  is  apparent  from  tlie  historical  review  which 
has  been  given,  it  was  important  for  us  to  determine  whether  changes  in 
the  walls  of  the  blood  vessels  are  a  factor  in  the  production  of  hemorrhagic 
infarction.  The  only  change  of  which  one  can  think  in  this  connection  is 
that  caused  by  insufficient  nutrition,  in  consequence  of  deficient  supply  of 
arterial  blood.  We  shut  out  for  variable  periods  of  time  parts  of  the  intes- 
tine from  the  circulation,  either  by  tying  tightly  rubber  tubing  around 
an  intestinal  loop  with  the  corresponding  mesentery,  or,  after  ligating  the 
intestine  and  all  its  vessels,  except  the  main  artery,  by  compressing  this 
artery  by  means  of  a  flat  rubber  clamp.  After  about  three  hours  peristalsis 
ceases,  and  camiot  be  reproduced  by  stimulation,  of  the  intestine.  If  then, 
or  even  at  a  later  period,  the  ligature  or  clamp  be  removed,  the  blood  at 
once  shoots  in  with  great  rapidity,  and  the  arteries,  veins,  and  capillaries, 
which  were  previously  shut  out  from  the  circulation,  become  distended  with 
blood.  As  a  rule,  during  the  period  of  ligation,  no  thrombosis  has  occurred 
8 


74  HEMORRHAGIC  INFARCTION 

in  the  vessels.  In  no  instance  in  which  the  veins  were  free  from  thrombi, 
were  we  able  to  produce  a  hemorrliagic  infarction  in  this  way.  Even  if, 
after  the  circulation  has  been  reestablished,  the  superior  mesenteric  artery 
be  ligated,  we  could  not  observe  that  the  hemorrhagic  infarction  appeared 
earlier,  or  was  more  intense  in  a  part  of  the  intestine  which  had  been  pre- 
viously deprived  of  its  circulation  for  three  or  four  hours,  than  in  the 
remainder  of  the  small  intestine.  Our  experiments  upon  this  point  were 
manifold,  and  afforded  no  evidence  in  favor  of  the  view  that  hemorrhagic 
infarction  is  in  any  way  dependent  upon  alterations  in  the  vascular  walls. 

In  view  of  the  observations  made  by  Cohnheim  upon  the  frog's  tongue, 
we  regarded  it  as  of  great  importance  to  devise  some  means  of  studying  the 
circulation  in  the  mesentery  under  the  conditions  in  which  hemorrhagic 
infarction  occurs.  Our  observations  upon  this  point  are  not  yet  completed. 
One  of  the  methods  which  we  adopted  was  a  modification  of  that  of  Ebertli 
and  Schimmelbusch.^  We  employed  an  electric  light  submerged  in  the 
salt  solution,  and  placed  beneath  the  stage  of  the  microscope  in  order  to 
illumine  the  object.  We  also  obtained  fairly  satisfactory  results  by  simply 
drawing  the  mesentery  out  over  a  glass  plate,  and  keeping  it  irrigated  with 
warm  physiological  salt  solution. 

Immediately  after  occlusion  of  the  superior  mesenteric  artery  the  circu- 
lation ceases  in  the  veins,  arteries,  and  capillaries  of  the  mesentery.  In  a 
very  short  time  the  circulation  returns  and  has  the  following  characters. 
The  arteries  contain  a  much  smaller  quantity  of  blood  than  normal,  and 
they  appear  contracted.  The  blood  flows  in  the  arteries  with  considerable, 
although  much  diminished,  rapidity  and  without  distinct  pulsation.  The 
movement  of  blood  in  the  veins  and  capillaries  is  sluggish  and  irregular. 
In  some  of  the  veins  the  direction  of  the  current  is  normal ;  in  others  it  is 
backward,  but  we  were  not  able  to  trace  the  regurgitant  flow  into  the  capil- 
laries. In  many  of  the  veins  and  capillaries  there  is  entire  cessation  of  the 
current.  Frequently  the  circulation  becomes  reestablished  in  vessels  where 
it  had  previously  ceased,  and  in  other  vessels  stasis  occurs.  The  distinction 
between  axial  and  plasmatic  current  is  obliterated.  Gradually  the  veins 
become  more  and  more  distended  with  blood,  and  these  as  well  as  many  of 
the  capillaries  become  filled  with  homogeneous  red  cylinders  of  blood.  Some- 
times the  red  corpuscles  become  clumped  together,  and  such  clumps  can  be 
seen  moving  in  the  veins.  We  also  noticed  frequently  clumps  of  white 
corpuscles  in  the  circulation.  The  extravasations  of  blood  took  place  chiefly 
from  the  small  and  medium  sized  veins,  but  also  from  the  capillaries,  and  at 
least,  in  part,  by  the  process  of  diapedesis.    The  microscopical  appearances 

"Eberth  u.   Schimmelbusch.     Virchow's   Archiv,  Bd.   103,   p.  57. 


HEMOEEHAGIC  INFAECTION  75 

in  the  veins  and  capillaries  resembled  those  seen  in  passive  congestion 
resulting  from  venous  obstruction,  and  yet  we  were  unable  to  discover 
coagula  in  the  larger  veins. 

I  have  now  presented  to  you  the  most  important  results  of  the  experi- 
ments which  we  have  thus  far  performed.  I  have  not  regarded  this  as  an 
appropriate  occasion  to  describe  in  detail  the  methods  employed,  or  to 
weary  you  with  the  minutiae  of  individual  experiments.  These,  together 
with  the  results  of  other  experiments  bearing  upon  this  question,  we  hope 
to  publish  in  more  complete  form  elsewhere. 
.     Our  experiments  justify  the  following  conclusions : 

1.  The  blood  which  produces  hemorrhagic  infarction  comes  from  the  col- 
lateral circulation  and  not  by  reflux  from  the  veins. 

2.  The  blood  pressure  is  very  low  in  the  region  where  hemorrhagic  infarc- 
tion is  taking  place  in  consequence  of  the  occlusion  of  the  main  artery. 

3.  If  the  force  of  the  arterial  and  capillary  circulation  sinks  below  a 
certain  point,   no  hemorrhagic  infarction  occurs. 

4.  There  is  no  evidence  that  changes  in  the  vascular  walls  are  concerned 
in  the  production  of  hemorrhagic  infarction. 

5.  Where  hemorrhagic  infarction,  resulting  from  arterial  obstruction,  is 
taking  place,  the  large  and  small  veins  are  distended  with  blood,  and  the 
arteries  contain  less  blood  than  normal.  The  circulation  is  sluggish  and 
irregular  in  the  veins  and  capillaries,  in  many  of  which  stasis  and  probably 
physical  alterations  in  the  red  corpuscles  occur. 

6.  The  hemorrhage  occurs  by  diapedesis. 

It  would  appear  that  hemorrhagic  infarction,  occurring  under  the  con- 
ditions described,  is  the  result  simply  of  mechanical  alterations  of  the  cir- 
culation, although  it  is  not  easy  to  give  an  entirely  satisfactory  mechanical 
explanation  of  all  of  the  phenomena.  We  should  remember  that  our  know- 
ledge of  the  dynamics  of  the  circulation  of  the  blood  is  still  imperfect.  We 
have  to  do  with  a  circulation  influenced  by  complicated  physiological  condi- 
tions, and  with  a  fluid  containing  solid  particles  of  complicated  physical 
properties. 

The  distention  of  the  veins  may  be  explained  by  the  insufficient  force 
with  which  the  blood  is  propelled  through  them.  This  force  is  so  feeble 
that  the  blood  corpuscles  cannot  be  pushed  through  them  as  rapidly  as  they 
are  sent  in  from  the  arteries  and  capillaries.  The  red  corpuscles  thus 
accumulating  in  the  veins  generally  block  them  up,  and  there  are  appearances 
which  speak  for  some  physical  alteration  in  the  red  corpuscles  when  thus 
massed  together.  When  many  of  the  veins  and  capillaries  are  thus  plugged 
with  stationary  or  feebly  propelled  colunms  of  red  corpuscles,  it  is  con- 


7G  HEMORRHAGIC  INFARCTION 

ceivable  that  a  pressure  far  below  the  normal  may  suffice  to  push  the  red 
corpuscles  through  the  vascular  walls,  inasmuch  as  their  progress  in  the 
normal  direction  is  im])eded.  That  the  character  of  the  tissue  surrounding 
the  vessels  is  an  important  factor  is  evident  from  the  more  rapid  occurrence 
and  greater  degree  of  the  hemorrhage  in  the  lax  mucous  than  in  the  dense 
muscular  coat  of  the  intestine. 

The  conclusions  which  we  have  drawn  from  our  experiments  apply  strictly 
only  to  infarction  of  the  intestine.  There  is,  apparently,  no  reason  why 
the  same  inferences  do  not  apply  to  hemorrhagic  infarctions  in  other  situa- 
tions. Still  the  conditions  should  be  investigated  separately  for  each  organ 
of  the  body  subject  to  hemorrhagic  infarction. 


EXPERIMENTAL  STUDY  OF  HAEMORRHAGIC  INFARCTION  OF 
THE  SMALL  INTESTINE  IN  THE  DOG ' 

The  experiments  described  in  this  paper  were  undertaken  to  determine 
the  circulatory  conditions  and  the  source  of  the  blood  in  the  production  of 
haemorrhagic  infarction,  the  time  of  onset  of  the  infarction,  as  well  as  other 
pertinent  factors.  In  order  to  subject  tliis  question  to  experimentation  it 
is  necessary  to  make  tests  upon  an  organ  in  which  haemorrhagic  infarction 
invariably  follows  occlusion  of  its  main  artery.  Furthermore  it  is  necessary 
that  the  vascular  system  of  the  organ  be  accessible  throughout  its  whole 
extent.  Both  these  requirements  are  present  in  the  small  intestine  of 
the  dog. 

Anatomy  and  Physiology. 

The  arteries  of  the  small  intestine  are  arranged  in  such  a  manner  that  the 
pressure  in  the  arterioles  of  the  d liferent  parts  of  the  intestine  is  practically 
the  same.  This  condition  of  things  exists  in  the  whole  small  intestine,  as  it 
is  supplied  with  a  single  arterial  trunk.  Soon  after  the  superior  mesenteric 
artery  leaves  the  aorta  it  passes  over  the  duodenum  and  forms  a  semicircular 
curve  between  the  two  layers  of  the  mesentery.  From  this  curved  vessel  the 
branches  to  the  intestine  arise — first  a  branch  to  the  duodenum  and  then 
branches  of  different  sizes  to  the  rest  of  the  small  intestine.  The  smallest 
of  these  branches  pass  directly  to  the  mesenteric  border  of  the  intestine, 
while  the  larger  divide  several  times  and  the  ultimate  twigs  of  all  anastomose 
to  form  a  single  series  of  mesenteric  arches.  From  these  arches  branches 
arise  about  every  half  centimeter,  pass  alternately  to  opposite  sides  of  the 
intestine  and  penetrate  the  muscle-wall  near  the  mesenteric  attachment,  to 
be  distributed  as  a  rich  plexus  (Heller's)  in  the  submucosa.  Before  these 
branches  (long  arteries)  pass  through  the  submucosa  they  give  rise  to  two 
or  three  twigs  which  anastomose  with  like  branches  from  their  neighbors, 
and  thus  form  an  arterial  plexus  just  outside  of  the  intestine.  From  this 
arterial  plexus  many  small  branches  arise  and  penetrate  the  muscular  coats 
at  right  angles  to  be  distributed  to  the  submucosa  of  the  mesenteric  side  of 
the  intestine.  The  arrangement  is  such  that  before  the  arteries  reach  the 
villi  there  are  three  distinct  sets  of  arterial  anastomoses;  the  arches,  the 
extraintestinal  plexus  and  Heller's  plexus  of  the  submucosa. 

*  William  H.  Welch  and  Franklin  P.  Mall.    This  paper,  written  in  1887,  has  not 
previously  been  published. 

77 


78  EXPERIMENTAL  STUDY  OF 

A  study  of  the  vessels  of  the  intestine  suggests  the  following : 

1.  Since  but  one  artery  supplies  the  intestine,  the  circulation  through  the 
intestine  depends  entirely  upon  the  pressure  at  the  beginning  of  the  superior 
mesenteric  artery. 

2.  Since  all  the  terminal  branches  of  the  superior  mesenteric  artery  are 
about  equally  distant  from  their  origin,  it  is  probable  that  with  a  given 
pressure  and  rapidity,  equal  parts  of  the  intestine  are  supplied  with  equal 
quantities  of  blood.' 

3.  The  fact  that  the  artery  divides  into  some  fifteen  branches,  and  these  in 
tuni  into  several  smaller  branches,  each  of  which  has  an  independent  muscu- 
lar coat,  makes  it  possible  that  a  simple  contraction  of  the  circular  muscle 
coat  at  any  point  can  mitigate  the  flow  of  the  blood  to  the  intestine  supplied 
by  the  arterial  branch.    This  statement  applies  to  the  smallest  arterioles. 

4.  The  rich  anastomosis  in  the  submucosa  aids  materially  to  equalize  the 
flow  through  the  mucosa  when  the  capillary  resistance  in  the  mucosa  is 
increased  or  diminished,  due  to  contraction  or  relaxation  of  the  muscularis 
mucosae  or  Bruecke's  muscle.* 

Our  experiments  were  performed  in  a  systematic  manner  to  determine  the 
following  question:  (1)  Through  what  channels,  under  what  pressure  and 
other  circulatory  conditions,  and  at  what  time  does  the  blood  enter  the 
vessels  to  produce  haemorrhagic  infarction  ?  (2)  These  factors  having  been 
determined  can  we  produce  haemorrhagic  infarction  of  the  intestine  by  other 
methods  than  ligation  or  complete  occlusion  of  the  main  arterial  branches? 
(3)  In  case  this  is  possible  in  the  living  animal  can  it  be  accomplished  also 
in  the  isolated  intestine  when  nourished  by  artificial  circulation  ? 

»A  more  careful  statement  would  probably  be  about  this:  If  we  consider  the 
intestine  to  be  divided  into  equal  parts,  a  to  z,  a  will  receive  m  amount  of  blood; 
\y,ffi  —  n;  c,  m  —  2n;  and  j,  m  —  25n,  being  much  less  than  half  of  rn.  This  state- 
ment is  more  nearly  correct  for  I,  as  one  passes  from  the  duodenum  down  to  the 
caecum  the  vessels  gradually  become  larger  and  longer.  2.  Injections  of  the 
intestine  first  fill  the  vessels  of  the  duodenum  and  then  those  lower  down  the  gut 
until  the  caecum  is  reached.  3.  During  digestion  fat  absorption  seems  to  take 
place  more  in  the  upper  part  of  the  intestine  and  diminishes  as  the  caecum  is 
approached.  4.  Haemorrhagic  infarction  after  ligation  of  the  superior  mesen- 
teric artery  is  as  a  rule  more  intense  in  the  duodenum  than  elsewhere.  But 
since  the  diameter  of  the  intestine  becomes  less  and  less  as  the  caecum  is 
approched,  it  is  reasonable  to  suppose  that  a  given  length  of  intestine  in  the 
duodenum  must  obtain  more  blood  than  the  same  length  nearer  the  caecum,  so 
ultimately  it  may  be  provided  that  a  villus  from  the  ileum  obtains  as  much 
blood  as  one  from  the  duodenum. 

'  For  a  more  detailed  account  of  the  blood-vessels  of  the  dog's  intestine  see 
Mall:  Blut.  u.  Lymphwege  im  Diinndarm  d.  Hundes.  Abhandl.  d.  K.  K.  Ges. 
d.  Wiss.,  Bd  XIV,  1887,  Leipzig. 


HAEMORRHAGIC  INFARCTION" 


79 


Ligature  of  the  Superior  Mesenteric  Artery.* 

Immediately  after  ligating  the  superior  mesenteric  artery  the  muscular 
walls  of  the  intestine  contract  and  become  anaemic.  This  condition  con- 
tinues for  some  three  to  four  hours,  when  the  intestinal  walls  gradually 
relax  and  the  mucous  membrance  becomes  first  hyperaemic  and  then  in- 
farcted,  the  process  extending  from  the  middle  of  the  duodenum  downward. 
The  infarction  is  complete  at  the  end  of  six  to  eight  hours ;  after  this  time 
its  intensity  is  not  generally  increased  as  the  excess  of  blood  now  leaves  the 
tissues  and  enters  the  lumen  of  the  intestine.  The  various  experiments 
upon  which  the  above  statements  are  made  are  given  in  Table  I. 


TABLE  I 
Condition  of  the  Intestine  after  the  Superior  Mesenteric  Artery  had  been 

LiGATED   for    3   TO    21    HOURS 


Experi- 
ment 

Duration 

of  the 

Condition  of  the  intestine 

Remarks 

experiment 

1 

3  hrs. 

Muscle    wall3  pale,  mucosa    hy- 
peraemic. 

2 

4     " 

Somewhat  more  hvperaemic  than 
No.  1. 

3 

5     " 

Hyperaemia  of  mucosa,  more  in- 
tense than  No.  2. 

4 

5     " 

Mucosa  of  parts  supplied  by  the 

The  artery  ligated  was  one  of 

artery  hyperaemic. 

the    large    branches    of    the 
superior  mesenteric. 

5 

5     " 

Infarction  of  the  entire  mucosa. 

6 

G     " 

a              <i       (C            (<                 ic 

7 

7     " 

ti              a      a           a                 a 

8 

7     " 

Infarction    more    intense     than 
No.  7. 

9 

12     " 

Complete   infarction   of    the   in- 

There was  much  blood  within 

testine. 

the  lumen  of  the  intestine. 

10 

21     " 

Cat.    The   infarction  is  mottled 

Considerable  blood  within  the 

and  not  complete. 

lymphatic  channels. 

11 

18     " 

Intestine    dilated     and     flabby; 

Intestine    filled  with  gas  and 

mucosa  very  haemorrhagic. 

blood. 

In  all  the  experiments  either  the  hyperaemia  or  the  infarction  begins 
abruptly  in.  the  middle  of  the  duodenum,  marked  by  the  junction  of  the 
superior  mesenteric  artery  and  the  pancreaticoduodenal  artery,  gradually 
becomes  somewhat  less  intense  as  the  caecum  is  approached  and  ends  very 


*  In  all  the  experiments  the  animals  were  anaesthetized  with  ether  or  ether 
and  morphia  combined. 


80  EXPERIMENTAL  STUDY  OF 

abruptly  in  the  middle  of  the  large  intestine  opposite  the  junction  of  the 
superior  and  inferior  mesenteric  arteries.  Not  only  is  the  infarction  some- 
what more  marked  in  the  upper  part  of  the  intestine  than  in  the  lower,  but 
it  also  begins  earlier  and  becomes  more  intense  in  the  villi  than  in  the 
intestinal  glands  (crypts),  the  rapidity  and  intensity  of  the  infarction  thus 
corresponding  in  both  instances  with  the  physiological  activity  of  these 
parts  when  viewed  from  the  standpoint  of  abfforption. 

After  the  infarction  is  complete  the  muscular  walls  of  the  intestine 
gradually  become  flabby  the  process  beginning  in  the  duodenum,  then 
gradually  extending  to  the  caecum.  The  intestine  dilates,  putrefaction 
takes  place  Avithin  the  lumen  and  gas  is  formed  which  gradually  distends 
the  walls  and  discolors  the  haemorrhagic  mucous  membrane.  Even  in 
extreme  states  of  relaxation  the  muscular  walls  are  not  necessarily  dead, 
for  they  often  respond  to  strong  irritants. 

What  has  been  determined  from  the  foregoing  experiments  regarding  the 
time  required  in  the  production  of  an  infarction  can  also  be  determined 
from  a  single  experiment.  After  ligature  of  the  superior  mesenteric  artery 
the  intestine  is  to  be  examined  from  hour  to  hour,  at  each  time  removing 
a  piece  of  it  in  order  to  examine  the  mucosa  as  well  as  for  comparison. 
Immediately  after  ligating  the  superior  mesenteric  artery  the  intestinal 
contractions  become  yery  active  and  continue  for  several  hours.  During  the 
third  hour  the  contractions  diminish  greatly,  the  veins  begin  to  dilate  and 
the  intestine  takes  on  a  bluish  tinge.  During  the  fourth  hour  the  intestine 
is  motionless  and  the  blueness  increases.  This  stage  is  followed  by  hyperae- 
mia  and  then  still  greater  hyperaemia  and  infarction.  The  same  result  is 
obtained  if  the  intestine  is  observed  by  the  method  of  Sanders  Ezn  and  van 
Braam  Houckgeest,  as  well  as  by  the  method  of  artificial  circulation  tlirough 
tlie  isolated,  but  living,  intestine. 

It  was  noted  in  the  foregoing  experiments  that  the  boundaries  of  the 
infarctcd  region  are  sharply  defined  by  the  distribution  of  the  branches  of 
the  artery  ligated.  To  test  this  question  in  detail  a  special  set  of  experi- 
ments was  made. 

LlGATURK  OF  BRANCHES  OF  THE   SUPERIOR  MESENTERIC    ArTERY. 

The  experiments  given  in  Table  I  show  that  the  anastomoses  with  the 
inferior  mesenteric  and  the  pancreatico-duodenal  arteries  are  not  sufficiently 
large  to  reestablish  the  circulation  through  the  intestine  after  the  main 
trunk  of  the  artery  has  been  ligated.  It  now  remains  to  determine  to  what 
extent  the  anastomoses  between  the  mesenteric  arches  can  reestiiblish  tlie 
circulation  when  a  nuiin  branch  of  the  superior  mesenteric  artery  has  been 
tied.     Furthermore  it  is  desirable  to  determine  to  what  extent  the  arterial 


HAEMORRHAGIC  INFARCTION 


81 


plexus  in  the  submucosa  can  re-establish  the  circulation  through  the  mucosa 
after  all  the  extra-intestinal  arteries  have  been  cut  off.  To  answer  this  sec- 
ond question  the  experiments  given  in  Table  II  were  made  (Fig.  1). 


TABLE  II 

Ligature  of  the  Main   Branches  of   the  Superior   Mesenteric   Arteries   as 
well  as  of  the  terminal  twigs  to  the  intestine 


Experi- 
ment 

Vessels  ligated 

Length  of 

the  loop  ol 

intestine 

cut  off  ' 

Duration 

of  the 

experiment 

Results 

12 

Mesenteric  branch  and  arches 
as  shown  in  Fig.  1,  c,  a',  a". 

13   cm. 

5hrs. 

Mucosa  opposite  branch 
ligated,  haemorrhagic. 

13 

Same  as  No.  12  with  an  addi- 
tional ligature  of  the  intes- 
tine at  a'. 

13      ■' 

5     " 

Mucosa  opposite  branch 
ligated  extremely  hy- 
peraemic. 

14 

As  No.  12 

fj      " 

1     5     " 

Mucosa  not  changed. 
Mucosa  hyperaemic. 

15 

5  long  intestinal  arteries  on 

2.5  " 

1     4     " 

either  side. 

IG 

4  long  intestinal  arteries   on 
either  side. 

2     " 

!     7     " 

•(                « 

17 

4  long  intestinal  arteries  on 
either  side. 

2     " 

4     .< 

Mucosa  not  changed. 

18 

3  long  intestinal  arteries   on 
either  side. 

1.5  " 

7     " 

Mucosa  hyperaemic. 

19 

3  long  intestinal  arteries  on 
either  side. 

1.5" 

4     w 

Mucosa  not  changed. 

20 

2  long  intestinal  arteries  an 
either  side. 

1 

7     " 

Mucosa  hyperaemic. 

21 

2  long  intestinal  arteries  on 
either  side. 

1 

1    7     " 

" 

22 

2  long  intestinal  arteries   on 
either  side. 

i      " 

:    7    " 

Mucosa  not  changed. 

23 

2  long  intestinal  arteries  on 
either  side. 

1           ** 

4     " 

*              ii                    u 

24 

1  long    intestinal    artery    on 
either  side. 

.5  " 

4     .. 

<<          ((              « 

25 

6  long  intestinal  arteries   on 
one  side. 

3      " 

4     .< 

X                U                      1< 

26 

5  long  intestinal  arteries  on 
one  side. 

2.5  " 

4     " 

27 

4  long  intestinal  arteries  on 
one  side. 

2      " 

4     " 

1(          ((              << 

28 

3  long  intestinal  arteries  on 
one  side. 

1.5  " 

4     .. 

29 

2  long  intestinal  arteries  on 
one  side. 

1      " 

4     « 

11          l(              << 

30 

1   long    intestinal    artery    on 
one  side. 

.5  " 

4     " 

Wliere  the  ligated  extra-intestinal  arteries  belonged  to  the  arches  it  was 
found  that  the  plexus  of  the  submucosa  is  sufficiently  large  to  reestablish 
the  circulation  through  the  mucosa  in  a  loop  of  intestine  5  cm.  long  but  not 


82 


EXPERIMENTAL  STUDY  OF 


large  enough  for  a  loop  13  cm.  long.  If  only  the  long  intestinal  arteries  are 
ligated  it  is  found  that  in  case  they  are  ligated  on  both  sides  of  the  intestine 
this  submucous  plexus  can  barely  reestablish  the  circulation  in  a  section  of 
intestine  1  cm.  long,  while  if  the  same  vessels  are  ligated  only  on  one  side 
of  the  intestine  the  lateral  anastomoses  as  well  as  those  of  the  submucosa  from 
the  opposite  side  can  easily  reestablish  the  circulation  through  a  loop  3  cm. 
long,  and  probably  much  longer.  These  two  groups  of  experiments  indicate 
the  presence  of  the  additional  set  of  anastomoses  (subintestinal  plexus)  be- 
tween the  mesenteric  arches  and  the  sul)mucous  plexus. 

In  order  to  determine  more  exactly  the  length  of  the  intestine  which  can 
be  nourished  through  the  submucous  plexus  and  mesenteric  arches  respec- 
tively the  experiments,  given  in  Table  III,  were  made.    The  idea  underlying 

TABLE  III 

Ligature  of  the  Bbaxches  of  the  Superior  Mesenteric  Artery  Including  the 
Duodenum,  with  or  without  Ligature  of  all.  of  the  Mesenteric  Arches 


Length 

Experi- 
ment 

Vessels  ligated 

of  the 
intestine 
experi- 
iTien-ted 

upon 

Duration 

of  the 

experiment 

Results 

31 

All  the    mesenteric 
branches  and    arches 
ligated   as    shown  in 
Fig.  1,  with  ligature 
of  the  duodenum. 

128  cm. 

5  hrs. 

The  mucosa  supplied  by  the 
artery  x^  is  infarcted,  that 
by  the  next  artery  x'  less 
infarcted  and  that  by  the 
third  artery  x"  is  hyperae- 
mic.  The  remainder  of  the 
mucosa  is  anaemic. 

32 

Mesenteric     branches 
and     the     duodenum 
including     its     arch 
ligated  as   shown    in 
Fig.  2. 

145    " 

6    " 

The  mucosa  supplied  by  the 
first  branch  is  unchanged, 
that  supplied  by  the  second 
branch  is  infarcted,  and  the 
rest  of  the  mucosa  is  anae- 
mic. 

33 

Same  a.i  No.  32 

120    " 

18    " 

The  mucosa  of  the  part  sup- 
plied by  the  first  branch  is 
hyperaemic,  that  of  the 
second  and  third  branches 
(12  cm.  long)  haemorrhagic, 
the  remainder  (90  cm.)  is 
necrotic. 

experiment  31  is  to  determine  the  change  in  the  mucosa  after  ligature  of  all 
the  arteries  entering  the  intestine  with  the  exception  of  tlie  submucous  plexus 
near  the  caecum,  as  shown  by  the  diagrammatic  Fig.  1.  The  result  in  this 
experiment  is  so  definite  that  it  at  once  gives  us  a  key  to  the  origin  of  the 
infarcted  blood,  at  the  same  time  refuting  completely  the  Cohnheim  doctrine 
of  venous  regursritation. 


HAEMORRHAGIC  INFARCTION  83 

Had  a  venous  regurgitation  taken  place  in  this  experiment,  then  the  whole 
mucosa  of  the  intestine  would  have  been  equally  infareted.  The  sharp  zone 
marked  by  the  degree  of  hyperaemia  in  the  mucous  membrane  shows  that  the 
origin  of  the  blood  is  not  from  the  veins,  as  the  veins  have  not  been  interfered 
with  in  any  portion  of  the  intestines.  The  zone  of  infarction  begins  sharply 
opposite  the  ligature  of  the  last  mesenteric  arch,  and  extends  equally  through- 
out the  mucosa  supplied  by  this  branch,  A\.  The  mucosa  supplied  by  the 
next  branch,  Xo,  is  very  hyperaemic,  while  that  of  the  third  branch,  A'j  is 
slightly  hyperaemic.    The  rest  of  the  intestine  is  anaemic. 

The  only  suitable  explanation  of  this  experiment  is  that  a  sufficient  quan- 
tity of  blood  entered  the  artery  X^  through  the  submucous  plexus  to  produce 
the  infarction  of  the  mucosa,  the  blood  being  equally  distributed  because  the 
pressure  as  well  as  the  quantity  of  blood  was  equalized  by  the  arterial  branch 
Xi  communicating  freely  with  all  parts  of  the  infareted  region.  The  second 
zone  received  its  flow  from  the  first  zone,  and  the  third  from  the 
second.  From  the  fourth  zone  onward  there  is  anaemia  as  the  heart-beat 
was  not  strong  enough  to  overcome  the  increased  resistance  of  more  than 
three  dilatations  in  the  arterial  bed,  produced  by  the  operation.  There- 
fore, a  certain  quantity  of  blood  is  required  for  normal  circulation,  less 
quantity  produces  haemorrhagic  infarction,  still  less  hyperaemia,  while 
finally  when  the  quantity  is  very  small  anaemia  and  necrosis  follow. 

While  experiment  31  determines  the  relative  extent  of  the  circulation 
through  the  mucosa  with  the  blood  entering  the  submucous  plexus,  experi- 
ments 32  and  33  (Fig.  2)  determine  it  with  the  blood  entering  through  the 
mesenteric  arches.  In  these  two  experiments  the  vascular  system  of  the 
intestine  is  reduced  to  series  of  mesenteric  arches  communicating  on  one 
end  only  with  the  main  trunk  of  the  artery.  The  experiment  shows  that  the 
first  arch  carried  a  sufficient  quantity  of  blood  to  the  mucosa  (20  cm.  long) 
of  the  first  system  to  re-establish  the  circulation  through  it.  The  second 
system,  however,  is  haemorrhagic;  the  remaining  systems  anaemic  and 
necrotic.  In  experiment  33  the  first  communicating  arch  is  a  very  tiny 
vessel,  and  the  first  zone  of  mucosa  is  not  haemorrhagic  but  hyperaemic, 
the  second  and  third  zones  are  haemorrhagic  and  the  remainder  of  the 
intestine  is  anaemic  and  necrotic.  So,  therefore,  these  experiments  show 
that  a  slight  diminution  of  blood  supply  produces  hyperaemia,  less  blood 
supply  haemorrhagic  infarction,  still  less  hyperaemia,  and  finally  if  the 
quantity  is  greatly  diminished  anaemia  and  necrosis  of  the  intestine. 

Combination  Experiments  Made  to  Show  the  Source  of  the  Blood  in 
Haemorrhagic  Infarction. 

If  it  is  true  that  the  blood  required  to  produce  an  haemorrhagic  infarction 
of  the  intestine  after  ligature  of  the  artery  enters  through  the  collateral 


84  EXPERIMENTAL  STUDY  OF 

arterial  branches  and  is  not  obtained  through  venous  regurgitation,  then 
ligature  of  tlie  vein  with  the  artery  must  increase  the  intensity  of  the  infarc- 
tion rather  than  diminish  it.  In  the  infarction  which  follows  ligature  of  the 
artery  the  blood  has  still  a  free  outlet  into  the  vein,  while  if  this  channel  is 
also  obstructed  the  infarction  must  be  intensified.  The  experiments  of  Cohn, 
of  Litten,  as  well  as  our  own,  support  this  view.  As  the  smaller  branches  of 
the  mesenteric  vessels  are  approached  the  veins  become  relatively  larger  and 
larger  and  therefore  tlie  ligature  of  a  peripheral  vein  with  its  artery  does 
not  intensify  the  infarction  so  much  as  the  ligature  of  a  larger  vein  with  its 
artery.  These  statements  which  are  drawn  in  a  general  way  from  the  experi- 
ments to  follow  point  towards  the  mechanical  explanation  of  haemorrhagic 
infarction.  Experiment  34  is  a  repetition  of  33  with  the  exception  that  the 
accompanying  veins  are  ligated  with  the  arteries.  In  this  experiment  the 
infarction  and  hyperaemia  of  the  mucosa  are  but  slightly  intensified  by  the 
ligature  of  the  veins  in  addition  to  the  arteries.  In  case  the  anastomoses  are 
smaller,  as  they  are  in  36  and  37,  including  the  veins  in  the  ligature  intensi- 
fies the  infarction. 

The  same  is  true  in  experiments  41  and  42,  as  well  as  all  the  experiments 
given  (Table  VII)  in  which  the  main  large  veins  were  ligated  with  the 
artery.  This  result  is  to  be  explained  by  the  ratio  between  the  sectional 
area  of  the  arteries  and  veins  not  occluded  in  the  experiment.  Fig.  4  is  the 
scheme  of  Experiment  34  (Fig.  3).  The  average  sectional  area  of  artery  a 
is  0.28  square  millimeters;  of  a'  0.032.  The  area  of  the  vein  v'  0.152.  In 
general  the  area  of  the  vein  is  five  times  that  of  the  accompanying  artery.  In 
case  the  veins  are  ligated  as  indicated  in  Fig.  4,  it  is  found  that  the  capil- 
laries of  the  mucosa  of  c'  and  c'  remain  normal ;  those  of  c^  become 
hyperaemic,  and  those  of  c*  and  cr'  become  haemorrhagic.  If  tlie  anastomos- 
ing arteries  are  considered  to  have  rigid  walls  the  relative  quantity  of  blood 
entering  these  capillaries  of  these  different  systems  would  be  for  c,  1/1 ;  c^, 

1/9;  r^,  1/9- ; c',  l/9-\     In  reality,  however  the  dilatation  of  the 

anastomosing  arteries  increases  this  quantity  considerably.  On  the  other 
hand  the  sectional  area  of  the  veins  being  at  least  five  times  that  of  the  accom- 
panying arteries  they  can  with  ease  carry  off  the  diminished  quantity  of 
blood  from  the  region  becoming  infarctcd  and  in  no  way  favor  stagnation. 
The  result  is  different  when  the  area  of  the  veins  more  nearly  reaches  that 
of  the  arteries,  as  in  the  case  of  the  submucous  plexus  and  in  the  very  large 
veins.  Here,  occlusion  of  the  veins  with  the  arteries  intensifies  the  degree 
of  the  infarction. 

All  the  necessary  experiments  to  produce  the  different  degrees  of  an 
infarction  can  be  performed  to  advant^ige  on  small  loops  of  intestine  as 
given  in  Fig.  G  and  Tabic  \'.    The  sectional  area  of  the  veins  of  the  sub- 


HAEMORRHAGIC  INFARCTION 


85 


mucosa  approaches  nearly  that  of  the  arteries,  so  this  factor  can  also  be 
included  to  advantage  in  making  the  different  experiments.  The  experi- 
ments together  point  toward  the  cause  of  the  infarction  in  the  showing  of 
the  normal  circulation. 

Given  the  proper  degree  of  stagnation,  the  greater  the  capillary  blood 
pressure  the  more  rapidly  is  the  infarction  produced  and  the  greater  is  its 
intensity.  In  case  the  artery  only  is  obstructed,  the  stagnation  of  circulation 
and  the  blood  pressure  must  be  pretty  definite  in  relation  to  production  of 
haemorrhagic  infarction,  for  a  slight  increase  or  diminution  of  these  two 
factors  is  followed  by  only  hyperaemia  (and  occasionally  oedema)  on  the 
one  hand,  or  anaemic  necrosis  on  the  other,  as  the  experiments  of  Tables  III 
and  IV  illustrate. 

TABLE  IV 

Combination  Experiments  Similab  to  those  Given  in  Table  III  with  the  Veins 
Included  with  the  Arteries 


Experi- 
ment 

Vesselg   ligated 

Length  of 
loops 

operated 
upon 

Duration 

of  the 

experiment 

Result 

34 

Both      mesenteric     ar- 
teries   and    veins    li- 
gated    as    shown    in 
Fig.  3. 

120  cm. 

7  hrs. 

Mucosa    of    first    and    second 
systems  apparently  normal ; 
third    system    hyperaemic; 
fourth,     fifth      and      sixth, 
haemorrhagic;    seventh    hy- 
peraemic,   and    8o    on,    see 

35 

All  of  the  arteries  and 
veins     including    the 
duodenum  and  ileum 
ligated   with   the  ex- 
ception  of  one  large 
arterial    branch   and 
its  vein  to  the  middle 
of    the    intestine    li- 
gated.   Only  through 
this    artery    could 
blood    reach    the    in- 
testine. 

5     " 

Fig.  3. 
The  part  of  the  intestine  sup- 
plied  by  the   patent  arteiy 
and    vein    were   apparently 
normal;      the     mucosa     on 
either  side  of   this   was  hy- 
peraemic;     the     remaining 
intestine    botli     above     and 
below      haemorrhagic,      the 
upper   part  being   more   in- 
tense than  the  lower. 

36 

Arteries  and  veins  with 
the    exception    of    a 
small  central  twig,  as 
indicated    in   Fig.  5, 

16  cm. 

7     " 

Mucosa  supplied  by  the  open 
artery  and  vein  normal,  with 
hyperaemia  on  one  side  and 
infarction    and   hyperaemia 

37 

No.  36,  ligated. 
Single  arterial  branch 
and  mesenteric  arches 
with     veins     ligated. 

7  " 

7     " 

on  the  other. 
Infarction,    although    not    in- 
tense throughout  the  entire 
mucosa  of  the  experimental 

3S 

Fig.  5,  No.  37. 
Experiment  like  No.  36 
excepting     that     the 
length  of  the  loop  of 
intestine    is    shorter. 
Fig.  5,  No.  38. 

6   " 

7     " 

region. 
Mucosa  unchanged. 

86 


EXPEKIMENTAL  STUDY  OF 


TABLE  V 

EXPE31IMENTS  UPON   LOOPS  OF  INTESTINE  FROM  5  TO  6  CM.  LONG   TO  TEST  THE  EFFECT 

OF  LiGATiNG  Different  Vessels  upon  the  Mucous  Membrane  of  the 

Lntestine.     The  Duration  of  the  Experiments  is  in  all, 

Instances  Six  Hours 


Experi- 
ment 

Vesiels  ligated 

Results 

39 

Both  venouB  and  arterial  arches  and  in- 
testine on  both  ends  ligated.     Fig.  6,  a. 

Mucosa  unclianged. 

40 

Artery    and    both    arterial    and    venous 
arches.     Fig.  6,  b. 

<(                (< 

41 

The  same  with  the  intestine   on   one  end 
ligated.     Fig.  6,  c. 

Mucosa  hyperaemic. 

42 

Artery  and  veins  and  arche*  with  intestine 

Complete  infarction   more  in- 

on one  end  ligated.     Fig.  6,  d. 

tense  near  intestinal  liga- 
ture. 

43 

The  same  as  above  witli   the  main  artery 
open.     Fig.  6,  e. 

Same  as  above. 

44 

Artery  and  vein  and  arches  ligated.     Fig. 

Complete     infarction    of    the 

6,/. 

mucosa,  being  sharply 
marked  above  and  below. 

45 

The  same  with  the  artery  open.    Fig.  6,  g. 

The  infarction  is  not  as  in- 
tense as  the  above  (No.  44). 

46 

All  the  veins  and  arteries  with  the  excep- 

Extreme infarction  of  the  in- 

tion of  the  main  artery  ligated.     Fig. 
6,  h. 
All  the  arteries  and  veins  with  the  excep- 

testine. 

47 

The     intestine      is      necrotic, 

tion  of  the  main  vein  ligated.    Fig.  G,  /. 

anaemic  and  Habby. 

Another  instructive  combination  in  tying  the  arteries  is  given  in  the 
experiments  of  Table  VI.    They  may  be  considered  as  experiments  within 


TABLE  VI 
ExPEaiiMENTS  Within  Experiments 


Experi- 
ment 


48 


40 


60 


Vessels  ligated 


Two  main  branches  and  pe- 
riplieral  arches  of  both 
arteries  and  veins  ligated. 
The  same  experiment  was 
then  performed  on  smaller 
vessels  in  tlio  middle  of  the 
first,  as  shown  in  Fig.  7. 

Ligature  of  the  superior 
mesenteric  artery  with  ad- 
ditional ligature  of  four  of 
its  main  branches  side  by 
side.     Fig.  8. 


Ligature  of  the  superior 
meeenteric  artery  as  well 
as  all  of  its  main  brandies. 


Duration 

of  the 

experiment 


4i  hrs. 


Results 


Infarction  of  the  entire  mucosa 
being  more  intense  opposite 
the  second  experiment  than 
elsewhere  (see  Fig.  7). 


Infarction  of  the  mucosa  of  the 
whole  small  intestine  with  the 
exception  of  50  cm.  near  the 
caecum.  The  infarcted  zone 
extends  into  the  part  supplied 
by  the  secondary  vessels  which 
have  been  ligated. 

Infarction  of  the  intestine  at  its 
upper  as  well  as  its  lower  end. 
The  middle  anaemic  /.one  is 
considerably'  longer  than  in 
Experiment  49. 


HAEMOERHAGIC  INFARCTION  87 

experiments.  In  case  the  inclosed  experiment  does  not  cover  a  great  area, 
as  shown  in  Fig.  7,  b,  the  infarction  in  it  is  intensified.  In  case  the  inclosed 
experiment  is  of  such  an  extent  that  by  itself  it  will  cause  intense  infarction, 
placing  it  within  another  experiment,  x,  results  in  diminution  of  the  infarc- 
tion. In  Experiment  49,  the  second  group  of  arteries  ligated.  Fig.  8,  x^ 
supplied  nearly  100  cm.  of  intestine,  about  enough  to  produce  an  infarction 
in  its  middle  50  cm.,  judging  by  Experiment  32,  Fig.  2.  Tying  the  main 
artery  in  addition  reverses  the  result  upon  the  loop  supplied  by  the  arteries 
marked  x^.  What  should  be  normal  upon  the  periphery,  beyond  a,  is  now 
haemorrhagic  and  what  should  have  been  haemorrhagic,  between  a  and  a, 
is  anaemic. 

After  making  these  experiments  upon  the  loops  of  the  intestine  to  deter- 
mine the  origin  of  the  blood  in  haemorrhagic  infarction  it  is  easier  now  to 
consider  in  an  intelligible  way  the  results  after  ligature  of  the  coarser  vessels 
of  the  intestine.  These  experiments  are  given  in  Table  VII;  they  can  be 
compared  to  advantage  with  those  given  in  Table  I.  In  Experiments  51  to 
56  the  inferior  mesenteric  artery  as  well  as  other  anastomoses  in  some  cases, 
were  left  open,  and  these  vessels  account  sufficiently  for  the  blood  required  to 
produce  the  infarction.  In  57,  however,  all  possible  circulation  through  the 
arteries  was  eliminated,  only  the  portal  vein  having  been  left  open ;  no  infarc- 
tion followed.  In  case  the  veins  alone  are  ligated  there  is  no  infarction  of 
the  intestine,  provided  the  anastomoses  are  sufficiently  large  to  carry  off  the 
blood.  As  the  veins  through  which  the  venous  blood  may  escape  are  ligated 
the  intestine  gradually  becomes  more  and  more  infarcted,  as  shown  in 
Experiments  62,  63  and  64. 

Under  certain  conditions  which  can  happen  only  in  an  experiment,  infarc- 
tion of  the  intestine  may  be  caused  by  venous  regurgitation.  In  Experi- 
ment 65  the  entire  root  of  the  mesentery  with  the  exception  of  the  inferior 
mesenteric  vein  was  ligated,  the  ligature,  of  course,  including  the  duodenum 
and  colon.  The  experiment  is  similar  to  No.  56.  The  extreme  infarction 
which  followed  must  have  been  caused  by  the  blood  which  entered  the  portal 
system  through  the  inferior  mesenteric  artery  and  vein.  In  this  experiment 
the  portal  pressure  was  soon  raised  to  the  arterial  and  an  infarction  fol- 
lowed, for  we  have  here  the  favorable  condition;  that  is,  stagnation  and 
pressure.  No.  66  is  a  similar  experiment  on  a  smaller  scale  (Fig.  9).  The 
arteries  and  veins  of  two  neighboring  loops  were  ligated  in  such  a  manner 
that  in  one  loop.  Fig.  9,  A,  there  was  high  arterial  pressure  with  the  veins 
ligated,  while  in  the  other  loop,  B,  high  venous  pressure  with  the  artery 
ligated.  In  both  loops  an  intense  infarction  followed.  When  the  artery  of 
the  loop  B  is  cut  open  at  E,  Fig.  9,  the  condition  in  this  loop  is  very  similar 
to  that  in  the  intestine  after  simple  ligature  of  the  superior  mesenteric 


88 


EXPERIMENTAL  STUDY  OF 


TABLE  VII 
Ligature  of  Different  Laroe  Arteries  and  Veins  of  the  Abdominal  Viscera 


Experi- 

Vessels ligated 

Duration 
of  the 

Uesulta 

ment 

experiment 

51 

Superior  mesenteric  artery  and 

10  hrs. 

Infarction    throughout   entire 

vein   and    inferior    mesenteric 

small  intestine. 

vein. 

52 

Superior  mesenteric  artery  and 

5     " 

Extreme  infarction  throughout 

portal  vein. 

the  small  intestine;    duode- 
num   and    stomach     hyper- 
aemic. 

53 

Coeliac    axis,    superior     mesen- 

6    " 

Extreme     infarction     of     the 

teric  artery  and  portal  vein. 

small  intestine. 

54 

The  same  aa  above 

6     " 
6     " 

Tiie  same  aa  above. 

55 

Coeliac    a\is,    superior    mesen- 

Infarction of  the  entire  intes- 

teric  artery,   portal   vein  and 

tine. 

duodenum     including     mesen- 

teric arch. 

56 

Coeliac    axis,     superior    mesen- 

3    " 

Infarction      of     intestine, 

teric   artery,   portal   vein  and 

stomach  and  spleen.     Fatty 

duodenum  and  ileum. 

metamorphosis  of  liver. 

57 

Whole   root   of   mesentery    with 
the  exception  of  portal  vein. 

10     " 

No  haemorrhagic  infarction. 

58 

Superior  mesenteric  vein. 

43     " 

No  infarction. 

59 

Superior    mesenteric    and    pan- 
creatico-duodenal  veins. 

21     " 

ti            (( 

60 

All   the  veins  of   a   loop    15   cm. 

12  days. 

Tlie  anastomosing  vein  dilated 

long  with  the  exception  of  one 

and  varicose. 

arcli. 

61 

The  same  as  Experiment  60 

4      " 

Coagulative     necrosis    and 
haeraorriiagic   infarction   of 
loop. 

62 

Superior    and     inferior     mesen- 

2i hrs. 

Mucosa    hyperaemic    and     in- 

teric  veins. 

farcted. 

63 

Superior      mesenteric,     inferior 

1  hr. 

Extreme    infarction  of    whole 

mesenteric     and    pancreatico- 

small intestine. 

duodenal  veins. 

64 

Portal  vein 

i  " 

Intestine  hyperaemic. 
Extreme  degree  of  infarction. 

65 

Root  of  mesentery  witli  tlie  ex- 

3 hrs. 

ception  of  tiie  inferior  me.'^en- 

teric. 

66 

The  vessels  and  intestine  of  two 

4     " 

The  loop  B  became  blue  first. 

intestinal  loops  ligated  as  in- 

and then  loop  A.    The  intes- 

dicated   in  Fig.  9.     The  circu- 

tine of  both  loops  was  inter- 

lation was  forced  to  take  the 

nally  haemorrhagic. 

direction  of  the  arrows. 

67 

The  same  as  above 

4     " 

The  same  as  above. 

68 

The  same  as  above  only  that  the 

4     " 

First  the  loop   A   became   hy- 

artery    was    cut     open    at     E 

peraemic,  then  the   loop   B. 

(Fig.  9). 

At  the  end  of  four  hours  the 
loop    A    was    very     haemor- 
rhagic; the  loop  B  was  less 
so. 
The  aame  as  above. 

69 

The  same  as  above 

4     " 

HAEMORRHAGIC  INFARCTION" 


89 


artery,  with  the  difference  that  the  direction  of  the  circulation  is  reversed. 
Under  these  conditions,  haemorrhagic  infarction  follows  (68  and  69). 

We  have  here  again  absence  of  the  pulse  wave,  retarded  circulation  and 
capillary  pressure,  factors  which  are  essential  in  the  production  of  an  infarc- 
tion, provided  there  is  no  obstruction  in  the  outflow  of  blood. 


Ligature  of  Either  Arteries,  Yeixs  or  Both,  at  the  Same  Time 
Reducing  the  Blood  Pressure  in  One  of  Them  to  Zero. 

The  results  obtained  by  ligating  the  different  vessels  in  the  study  of 
haemorrhagic  infarction  are  in  general  confirmatory  of  those  obtained  by 
Cohn  some  forty  years  ago.  In  order  to  gain  a  deeper  insight  of  this  ques- 
tion it  is  necessar}'  not  only  to  study  the  vessels  from  without  but  also  from 
within. 

The  first  experiments  we  performed  to  study  the  blood  pressure  in  the 
intestine  during  the  production  of  an  infarction  are  given  in  Table  VIII. 

TABLE  VIII 

Experiments  Made  to  Produce  Haemorrhagic  Infarction  of  a  Loop  of  Intestine 
AT  THE  Same  Time  Opening  Either  the  Artery,  the  Vein  or  Both 


Experi- 
ment 

Vessels  ligated 

Vessels 
opened 

Length 

of  the 

loop  of 

intestine 

Duration 

of  the 
expeciment 

Results 

70 

71 

72 

Artery  and  mesenteric 
arches. 

Artery,  vein  and  mesen- 
teric arclies. 

The  same 

Artery. 
None. 

Artery 
and 
vein. 

None. 

u 

Vein. 

Artery. 

None. 

Artery. 
Vein. 

8  cm. 
8    " 

8    " 

12    " 
12    " 
12    '« 
12    " 
10    " 

10   " 
10    " 

4  hrs. 
4     « 

4  " 

10    "(?) 
10    "(?) 
10    «(?) 
10    "(?) 

5  " 

5    " 
5    " 

Mucosa  not  changed. 

Mucosa   hyperaemic. 

Mucosa    slightly   hy- 
peraemic. 

Mucosa    haemor- 
rhagic. 
The  same. 

Mucosa  very  haemor- 
rhagic. 

Mucosa  oedematous 
and  somewhat 
haemorrhagic. 

Mucosa    haemor- 

73 
74 
75 
76 
77 

78 

Artery  and  arches  .... 

Artery,  vein  and  arches. 

((           <(       <(         « 

Artery,     vein,     mesen- 
teric   arches  and  in- 
testine on  one  side. 

The  same 

79 

«         <( 

rhagic. 
The  same. 

In  these  experiments  the  pressure  in  either  the  artery  or  the  vein  was  re- 
duced to  zero  by  simply  opening  a  branch  of  either  of  them  after  ligature  of 
the  main  trunk. 


90  EXPEKIMENTAL  STUDY  OF 

It  is  fair  to  a^ume  that  when  an  arterial  or  venous  branch  is  cut  open 
and  constantly  observed,  to  see  that  it  is  bleeding  freely  and  does  not  become 
plugged  with  clots,  the  pressure  within  it  will  fall  nearly  to  zero.  As  the 
average  pressure  in  the  vena  porta  is  usually  6  mm.  Hg.,  reducing  the  pressure 
to  zero  after  the  artery  has  been  ligated  should  have  little  effect  upon  the 
production  of  the  infarction  as  is  proved  to  be  the  case.  On  the  other  hand, 
reducing  the  arterial  pressure  to  zero,  as  in  Experiments  70,  76  and  78,  no 
infarction  should  follow,  but  in  some  of  these  experiments  the  intestine 
became  more  haemorrhagic  than  it  would  have  been  had  the  artery  not  been 
opened.  The  result  in  these  three  experiments  is  not  uniform;  in  lO,  in 
which  the  vein  was  not  operated  upon,  the  intestine  did  not  even  become 
hyperaemic,  while  in  76  and  78  in  which  the  veins  were  also  ligated  the 
intestine  became  haemorrhagic.  In  Experiments  75  and  76,  which  were 
done  under  like  conditions  upon  the  same  animal,  the  veins  were  not  opened 
until  the  loops  had  become  very  hyperaemic,  due  to  the  ligatures  which  had 
been  applied.  Opening  the  vein  (75)  relieved  this  hyperaemia  at  once, 
while  opening  the  artery  (76)  made  no  perceptible  effect  upon  it.  In  this 
point  of  difference  may  be  the  key  to  the  cause  of  the  intensified  infarction 
after  ligature  of  both  artery  and  vein  with  the  arterial  pressure  reduced  to 
zero.  To  test  this  question  a  step  further.  Experiments  77,  78  and  79  were 
made  under  like  conditions  upon  the  same  animal.  In  Experiment  78  tlie 
blood  flowed  from  the  cut  end  of  the  artery  at  the  rate  of  3.5  c.  c.  per  hour, 
and  out  of  the  cut  vein  at  the  rate  of  43  e.  e.  per  hour,  confirming  what  was 
observed  regarding  the  hyperaemia  in  Experiments  75  and  76.  The  blood 
which  produces  the  infarction  in  the  above  experiments  can  enter  the  loops 
only  through  the  submucous  arterial  plexus.  And  it  is  very  remarkable  that 
under  these  conditions  it  appears  easier  for  blood  to  pass  over  from  the  sub- 
mucous arterial  plexus  through  the  capillaries  than  simply  backwards  and 
out  of  the  opened  artery.  Other  factors,  as  constriction  of  the  artery  due  to 
contraction  of  its  muscular  coats  when  the  blood  pres.=5ure  is  low,  or  as 
muscular  contractions  of  the  walls  of  the  intestine,  may  play  a  role  in  this 
remarkable  experiment.  Under  certain  conditions  the  contractions  of  the 
muscular  coats  of  the  intestine  accelerates  the  circulation  through  its  wall 
to  such  a  marked  degree  that  the  venous  pressure  may  exceed  the  arterial.' 
This  condition  is  also  observed  in  Experiment  82.  Until  the  normal  circu- 
lation through  the  intestine  is  more  thoroughly  understood  it  will  remain 
difficult  to  explain  Experiments  76  and  78. 

'  Mall:    Johns  Hopkins  Hospital  Reports,  I,  p.  54. 


HAEMORKHAGIC  INFARCTION 


91 


Blood  Pressure  in  the  Arteries  and  Veins  of  the  Intestine  During 

THE  Production  of  an  Haemorrhagic  Infarction  After 

Ligature  of  the  Superior  Mesenteric  Artery. 

The  experiments  given  in  Table  VIII  indicate  that  it  is  essential  to  record 
the  pressure  in  the  distal  end  of  the  superior  mesenteric  artery  after  the 
main  branch  has  been  ligated,  during  the  production  of  an  infarction.  In 
the  experiments  recorded  in  Table  IX  cannulae  were  introduced  into  a 

TABLE  IX 

Blood  Peesstjbe  in  the  Distal  Ends  of  the  StirERioB  Mesentbibic  Abtexy  and 
Vein  ajfteb  Ligation  of  One  ob  Both  of  these  Vessels 


VfBsel  ligated 

Blood  pressure  in  mm.  Hg. 

Duration 

of 

experiment 

Experi- 
ment 

Before 

ligature 

Alter 
ligature 

Result 

Artery 

Vein 

Artery 

Vein 

80 
81 

Superior 

mesenteric 

artery. 
Artery     and 

128 
131 

7 

29 
30 

8 

5  hre. 
4    " 

Infarction  of  the  entire 
mucosa. 

The  same. 

82 

vein. 
Artery,    vein 
and  pancre- 
atico-duo- 
denal. 

60 

25 

9 

Extreme  infarction.  In 
the  first  part  of  the 
experiment  the  pres- 
sure in  the  artery  and 
vein  is  given  for  every 
10  minutes.  After  the 
first  hour  it  was  more 
irregular. 

branch  of  the  superior  mesenteric  artery  and  vein,  pointing  centrally.  Then 
the  main  trunks  were  ligated.  The  pressures  were  recorded  upon  the  moving 
drum  and  the  cannulae  and  intestines  observed  during  the  entire  experiment. 
After  ligature  of  the  artery  tlie  intestine  became  very  irritable  and  pale 
and  remained  so  into  the  third  hour.  Then  it  gradually  became  quiet  and 
hyperaemic  the  infarction  taking  place  during  the  fourth  and  fifth  hours. 
Immediately  after  ligature  of  the  artery  the  pressure  in  both  the  artery  and 
vein  fell  to  its  lowest  point.  In  the  course  of  five  minutes,  however,  the 
pressure  gradually  rose  and  remained  stationary  during  the  whole  experi- 
ment. In  Experiments  80  and  81  the  arterial  pressure  fell  to  about  one- 
fourth  the  normal  after  ligature  of  the  artery.  In  82  the  venous  outflow 
was  completely  obstructed  so  the  pressure  in  the  artery  gradually  rose,  but 
the  venous  pressure  rose  more  rapidly  and  at  one  time  exceeded  the  arterial. 
The  infarction  followed  very  rapidly.    These  few  experiments,  together  with 


92 


EXPERIMENTAL  STUDY  OF 


many  others,  show  that  a  considerable  blood  pressure  is  present  in  the  pe- 
ripheral end  of  the  artery  after  its  ligation,  while  haemorrhagic  infarction  is 
taking  place,  and  Experiments  80  and  81  fix  this  pressure  at  one-fourth  the 
normal. 

Pkoduction  of  Haemorrhagic  Infarctiox  of  the  Intestine  by  Partly 

Occluding  the  Superior  Mesenteric  Artery  After  all 

the  Anastomoses  Have  Been  Ligated. 

In  case  the  initial  cause  of  the  infarction  which  follows  ligature  of  the 
superior  mesenteric  artery  is  simply  reduction  of  the  arterial  pressure,  then 
infarction  should  always  result  when  the  arterial  pressure  is  reduced  by 
other  means  than  by  tying  the  main  artery.  This  view  is  substantiated  by 
the  experiments  recorded  in  Table  X. 


TABLE  X 

Experiments  in  which  the  Arterial  Pressure  was  Reduced  by  Clamping  the 

Main  Trunk  of  the  Superior  Mesenteric  Artery  after  Ligature  of 

ALT.  OF  ITS  Arterial  Anastomoses  Including  the  Intestine 

Above  and  Bexow 


Experi- 
ment 

Vessel  clamped 

Degree  of  clamping 

Duration 
of 

Result 

clampiag 

83 

Superior  mesenteric 

Arterial  pressure  re- 

3 hrs. 

Mucosa    very    hyper- 

artery. 

duced  to  i  30  mm. 

aemic. 

84 

Artery    to    loop    of 
intestine. 

Until    pulse    nearly 
disappeared. 

6     " 

Mucosa  hyperaemic. 

85 

The  Bame 

Until    pulse     disap- 
peared. 

6     " 

Mucosa     hyperaemic 
and  infarcted. 

86 

<(        i( 

The  same 

6     " 

Mucosa  liyperaemic. 
Infarction. 

87 

«         « 

((            sc 

6     " 

88 

All  arterial  anasto- 
moses    tied      and 
clamp  on  superior 
mesentfric  artery. 

«           « 

8     " 

Extreme    haemor- 
rhagic infarction. 

89 

The  same   

«           f< 

8     " 

The  same. 

In  making  the  experiments  the  main  artery  and  vein  were  isolated  and 
all  of  the  remaining  tissues  at  the  root  of  tlie  mesentery-,  including  the  duo- 
denum and  colon,  were  ligated.  By  this  method  the  blood  entered  the 
intestine  throngli  tlio  main  stem  of  the  artery  only.  The  same  precautions 
were  employed  when  experimenting  upon  a  loop  of  intestine.  In  this  experi- 
ment it  is  necessary  to  clamp  the  main  trunk  of  the  artery  in  such  a  manner 
that  no  kinking  is  i)()ssihle  to  obstruct  the  circulation  entirely.     This  was 


HAEMOREHAGIC  INFARCTION  93 

accomplished  by  a  double-screw  clamp  encircling  the  artery  with  a  thick- 
walled  rubber  tube  4  mm.  in  diameter  and  10  cm.  long  on  either  side  of  it. 
In  screwing  down  the  clamp  most  of  the  force  was  spent  in  compressing  the 
rubber  tube,  thus  making  the  clamp  firm.  The  length  of  the  rubber  tube 
kept  the  clamp  in  place.  By  this  method  of  constricting,  the  artery  lies  in 
a  firm  slot  which  cannot  kink  it. 

The  degree  of  constriction  of  the  artery  was  regulated  in  Experiment  83 
by  measuring  the  pressure  in  the  distal  end  of  the  artery.  The  clots  which 
formed  in  the  cannula  were,  however,  very  troublesome,  so  another  method 
of  determining  the  proper  reduction  of  arterial  pressure  was  employed.  In 
all  of  the  experiments  in  which  the  superior  mesenteric  artery  was  ligated 
it  was  observed  that  there  was  no  detectable  pulse  wave  in  the  arteries  of  the 
mesentery.  The  same  was  true  in  Experiment  83.  So  in  most  of  the  experi- 
ments given  in  the  table,  the  main  artery  was  compressed  until  the  pulse 
wave  in  the  distal  branches  had  just  disappeared.  A  small  branch  was  then 
cut  open  and  it  was  found  that  the  blood  oozed  out  of  it  drop  by  drop,  as  it 
did  from  the  one  cut  in  Experiment  83.  By  this  method  not  only  was  the 
pressure  of  the  artery  quickly  reduced,  but  the  pulse  wave  was  also  arrested. 

The  result  of  Experiments  84,  85  and  86  was  not  as  satisfactory  as  was 
expected  beforehand,  but  in  87,  88  and  89  the  infarction  was  in  every  respect 
as  intense  as  could  be  obtained  by  ligature  of  the  main  trunk  with  the 
anastomoses  open.  Furthermore  there  was  a  great  quantity  of  blood  within 
the  lumen  of  the  intestine  of  Experiments  88  and  89. 

These  experiments,  as  all  others,  indicate  that  in  the  production  of  an 
haemorrhagic  infarction  the  rapidity  of  the  circulation  through  the  capil- 
laries is  greatly  diminished.  In  infarctions  following  partial  occlusion  of 
the  artery,  the  circulation  is  sufficiently  slow  to  produce  infarction  when  the 
arterial  pressure  is  reduced  to  one-fourth  the  normal,  which  is  also  just  the 
point  at  which  the  perceptible  pulse  wave  is  lost. 

Experiments  Made  to  Test  the  Effect  of  Ischaemia  Upon 
Haemorrhagic  Infarcation. 

It  is  observed  in  the  foregoing  experiments  that  a  very  definite  period  of 
lime  elapses  after  ligature  of  the  superior  mesenteric  artery,  or  its  branches, 
before  the  beginning  of  haemorrhagic  infarction.  After  diapedesis  is  well 
started  the  further  progress  of  the  infarction  is  fairly  rapid.  These  facts 
induced  Virchow  to  suspect  that  capillary  necrosis  is  caused  by  the 
ischaemia,  thus  favoring  the  escape  of  blood  into  the  tissues.  This  idea  in 
turn  served  as  a  basis  for  Cohnheim's  theory,  who  in  addition  accounted  for 
the  necessary  blood  through  venous  regurgitation.    The  experiments  which 


94 


EXPERIMENTAL  STUDY  OF 


follow  contradict  the  idea  that  capillary  necrosis  plays  any  role  whatever  in 
the  production  of  haemorrhagic  infarction. 

Table  XI  gives  a  group  of  experiments  in  which  either  the  whole  intestine 
or  one  of  its  loops  was  deprived  entirely  of  arterial  blood  for  from  30  minutes 
to  3  hours,  after  which  the  circulation  was  reestablished. 


TABLE  XI 

EXPEBIMEXTS    IN    WHICH    THE    ISCHAEMIC    INTESTINE    WAS    FOLLOWED     BY    Re- 
ESTAHLISHMEM    OF    THE    ClBCULATION 


Experi- 
ment 

First  operation 

Duration. 

Second 
operation 

Duration 

Result 

90 

Ischaemia  of  a  loop  of 

A  hr. 

Circulation 

20  hrs. 

Intestine  appar- 

intestine. 

reestab- 
lished. 

ently  normal. 

91 

The  same 

2i  hrs. 

The  same. 

20    " 

8    " 

The  same. 

92 

Ischaemia  of  entire  in- 

«       it 

testine. 

93 

Ischaemia  of  a  loop  of 
intestine. 

2h  " 

(•         « 

3    " 

Mucosa  slightly  hy- 
peraemic. 

94 

The  same 

3      " 

It         (< 

3    " 

Mucosa  apparently 
normal. 

95 

The    same.      The    vein 
was  not  closed. 

3      " 

((         ti 

3    " 

The  same. 

96 

Ischaemia  of  entire  in- 
testine.   The  superior 
mesenteric    vein  left 
open. 

3      " 

U                 tl 

3    " 

((         tt 

97 

Loop     of     intestine 
ischaemic.   Main  vein 
was  left  open. 

3      " 

<(           « 

2    " 

It        tt 

In  making  these  experiments  all  possible  anastomoses,  including  those 
through  the  intestinal  walls  were  first  ligated,  after  which  the  main  artery 
and  vein  was  compressed  by  tying  it  between  two  blocks  of  rubber.  In  every 
experiment  a  small  arterial  twig  of  the  mesentery  was  opened  immediately 
after  clamping  tlie  main  artery,  and  before  as  well  as  after  the  renewal  of  the 
clamp,  in  order  to  determine  the  condition  of  the  circulation  in  the  experi- 
mental loop.  In  all  cases  it  was  found  that  the  method  is  satisfactory,  for 
in  no  instance  were  we  troubled  with  clot-formation  either  in  the  artery  or 
the  vein.  It  was  also  found  that  after  several  hours  of  ischaemia  the  intes- 
tine was  quiet  and  would  barely  respond  to  irritants.  Under  this  condition 
reestablishing  the  circulation  wiis  followed  by  a  gush  of  blood  through  the 
arteries  over  into  tht*  veins,  the  intestine  at  the  same  time  becoming  very 
hyperaemic. 


HAEMORRHAGIC  INFARCTION 


95 


In  no  instance,  however,  did  haemorrhagic  infarction  follow.  In  Experi- 
ments 95,  96  and  97  the  vein  was  not  included  in  the  clamp  in  order  to  give 
the  "  venous  reflux"  every  possible  chance  in  the  production  of  the  infarc- 
tion.   Yet  the  result  here  was  also  negative. 

In  the  second  group  of  experiments,  Table  XII,  a  loop  of  intestine  was 


TABLE  XII 

ISCHAEMIA  OF  THE  INTESTINE  FOLLOWED  BY   Rf:ESTABLISHMENT    OF    THE    ClBCirLATION 
AND    LlGATUKE  OF   THE   SUPEailOB   MESENTERIC   ABTEEY 


Experi- 
ment 

First  operation 

Duration 

Second 
operation 

Duration 

Result 

98 

Ischaemia    of    loop    of 

2i  bra. 

Superior 

12  hrs. 

Loop    no   more    in- 

intestine. 

mesenteric 
ligated. 

farcted  than  the 
rest  of  the  mucosa. 

99 

Tlie  same 

3     " 
3     " 

The  same.  . 

li                 'C 

5     " 
5      " 

The  same. 

100 

a             a 

(<        (. 

101 

Ischaemia  of   loop  and 
vein  cut  open. 

3     " 

(<           <( 

15     " 

Mucosa  of  loop  less 
infarcted  than  rest 
of  intestine. 

102 

Ischaemia    of    loop    of 

3     " 

The    same 

4     " 

Loop  more  infarcted 

intestine. 

and   por- 
tal    vein 
ligated. 

than  mucosa  of 
immediate  neigh- 
borhood, but  not 
as  much  as  that 
of  duodenum. 

103 

Ischaemia    of    loop    of 

2i    " 

Ligature 

8i    " 

Mucosa      with     the 

intestine  with  an  ad- 

removed 

exception   of    loop 

ditional    ligature 

from  loop. 

extremely  haemor- 

around  the    superior 

rhagic. 

mesenteric  artery. 

first  made  ischaemic  for  a  number  of  hours,  after  which  the  circulation  was 
reestablished  in  order  to  exclude  the  possibility  of  clot-formation  within  the 
vessels  of  the  experimental  loop.  As  soon  as  this  possibilit}'  was  excluded  the 
superior  mesenteric  artery  was  ligated.  In  this  group  of  experiments  a  loop 
of  the  intestine  was  ischaemic  some  hours  longer  than  the  rest  of  the  intestine, 
and  therefore  if  ischaemia  is  favorable  to  the  production  of  an  infarction 
that  in  the  loop  should  be  increased.  With  the  exception  of  103,  this  was  not 
the  case. 

In  fact,  there  seemed  to  be  a  tendency  for  the  experimental  loop  to  be  less 
infarcted  than  the  remaining  intestine.  It  may  be  of  some  value  to  add  a 
note  regarding  Experiment  102.  After  the  clamp  was  removed  from  the 
vessels  of  the  experimental  loop  the  intestine  became  very  hyperaemic. 
Ligature  of  the  superior  mesenteric  artery  was  followed  by  anemia  and 


96 


EXPERIMENTAL  STUDY  OF 


violent  contraction  of  the  whole  intestine  with  the  exception  of  the  loop. 
Next,  the  portal  vein  was  ligated  and  then  the  intestine  became  much  bluer 
than  the  loop. 

In  the  third  group  of  experiments  the  proper  vessels  were  clamped  for  a 
sufficient  length  of  time  to  produce  an  infarction  after  which  the  circulation 
was  reestablished.  The  test  in  these  experiments  is  to  determine  whether 
an  "  ischaemia/'  under  which  an  infarction  does  follow,  favors  increased 
infarction  in  case  the  blood  pressure  is  increased.  The  result  was  again 
decidedly  negative.  When  the  clamp  was  removed  from  the  main  artery  its 
branches  began  to  pulsate,  and  the  blue  intestine  became  pink  as  the  blood 
shot  through  its  veins.  It  appears  as  if  the  infarction  is  at  once  washed 
out  instead  of  becoming  increased,  and  in  the  course  of  from  10  to  20  hours 
the  condition  of  the  intestine  is  nearly  normal  in  appearance. 

TABLE  XIII 

Vessels  Clamped  a  Sufficiently  Long  Time  to  Produce  ax  I.nfarctiox  after 
WHICH  Reestablishing   the  Circulation  Washed  it  Out 


Time 

between 

removing 

Experi- 
nient 

Vessels  clamped 

Duration 

Condition 
of  loop 

the  clamp 
and 
ending 
the  ex- 
periment 

Result 

104 

Artery    of    large    loop 

4  hrs. 

Loop  very  hy- 

20  hrs. 

Hyperaemic   spots 

clamped. 

peraemic. 

in  mucosa  of 
loop. 

105 

Superior  mesenteric 
artery. 

6i  " 

The  same  . .  . 

Infarction. 

lOG 

Superior  mesentericand 
j)ancreatico-duodenal 
arteries. 

4     " 

20  hrs. 

Slight  infarction. 

107 

Artery    and    arclies    of 
loo[)  35  cm.  long. 

5i  " 

10   " 

Mucosa  slightly 
hyperaemic. 

108 

Arteries    and    veins   of 
large  loop. 

4     " 

17   " 

The  same. 

109 

Artery  and  vein  to  loop 
20  cm.  long. 

5J" 

10   " 

Mucosa  normal. 

110 

Artery,  vein  and  mesen- 
teric arches  to   large 
loo[). 

4     " 

20   " 

Mucosa  necrotic 
iiud  of  brownish- 
red  color. 

111 

Artery  and  vein  of  loop 
20  cm.  long. 

5J  " 

10   " 

Mucosa    but 
sliglitly  tinged. 

112 

Vein     and     mesenteric 
arches  of  loop  20  cm. 
long. 

5i  " 

10   " 

Mucosa  somewhat 
more  colored 
than  tliat  in  im- 
mediate neigh- 
borhood. 

HAEMOERHAGIC  INFARCTIOX 


97 


The  Production  of  Haemorrhagic  Infarction  in  the  Isolated 
Intestine  with  Artificial  Circulation. 

The  experiments  made  upon  the  intestine  within  the  living  animal 
indicate  that  the  cause  of  haemorrhagic  infarction  after  ligature  of  the 
superior  mesenteric  artery  is  not  to  be  found  in  the  necrosis  of  the  capillaries 
nor  in  venous  regurgitation,  but  in  physical  conditions  within  the  blood 
stream  itself,  due  to  a  slowing  of  the  circulation  with  absence  of  an  arterial 
pulse  wave. 

In  case  this  ie  true,  artificial  circulation, through  the  isolated  intestine 
with  whipped  blood  imder  a  low  but  constant  pressure  will  result  in  haemor- 
rhagic infarction,  provided  that  an  important  factor  does  not  lie  in  the 
difference  between  whipped  and  normal  blood.  The  experiments  given  in 
Table  XIV  show  that  with  the  circulation  in  the  isolated  intestine  similar  to 


TABLE  XIV 

expebiments  in  which  artificial  c1rcui.ation  was  carried  on  through  the 

Isolated  Intestine  with  Whippeu)  Blood  Diluted  with  Normal 

Saline  Solution  at  37°  C. 


Experi- 

Arterial 

Venous 

Duration 
of  ex- 

Note 

Result 

ment 

pressure 

pressure 

periment 

113 

0-120 

0-30 

1  hr. 

Hyperaemia. 

Loop  with  rythmic  con- 

114 

66 

0-40 

35  min. 

Rythmic      contractions 

of  a  large  loop  while 

tractions  hyperaemic ; 

venous   pressure  was 

rest     of     intestine 

high. 

haemorrhagic. 

115 

0-93 

0-50 

1  hr. 

Vermicular        contrac- 
tions active. 

Haemorrhagic       infarc- 
tion. 

116 

100 

7 

20  min. 

No  blood  came  from  the 
vein. 

The  same. 

117 

15 

8 

4^  hrs. 

Intestine      handled      a 
great  deal. 

Spotted  infarction. 

118 

10-80 

10 

51    " 

The  same 

Hyperaemia. 
No  infarction. 

119 

65 

4 

4i    " 

Vermicular        contrac- 

tions active. 

120 

27 
40-65 

7 
4 

4i    " 
5      " 

Infarction. 

121 

Parallel     experiments. 

Hyperaemia.     Intestine 

Neither  specimen  dis 

contracted. 

turbed. 

122 

20-35 
65 

1 

1 

5      " 

4i    " 

The  same 

Infarction. 

123 

Parallel       experiments 

Hyperaemia. 

on      two     specimens 

which  had   been  pre- 

served  upon    ice    for 

48  hours. 

124 

20 

1 

4i    " 

The  same 

Infarction. 

98  EXPERIMENTAL  STUDY  OF 

that  in  the  intestine  after  ligature  of  the  superior  mesenteric  artery,  haemor- 
rhagic  infarction  takes  place  very  rapidly. 

It  has  been  found  that  the  muscular  walls  of  the  intestine  show  great 
activity  in  the  isolated  intestine  for  a  number  of  hours  after  its  removal 
from  the  body,  provided  it  is  nourished  with  blood  through  its  arteries  and 
is  kept  at  normal  body  temperature.  The  short  time  which  elapses  (this 
need  not  exceed  five  minutes)  while  the  intestine  is  being  removed  from  the 
animal  to  the  warm  chamber  does  not  seem  to  affect  this,  for  in  experiments 
made  in  this  way  the  activity  of  the  contraction  of  the  muscular  walls  is  as 
vigorous  as  when  the  artificial  circulation  is  established  before  the  normal 
is  broken. 

In  performing  the  operation  the  only  precaution  necessary  is  to  ligate 
the  duodenum  and  colon  with  their  mesenteric  arches  and  then  cut  out  the 
whole  intestine  with  an  abundance  of  the  root  of  the  mesentery.  The  can- 
nulae  and  the  rest  are  easily  applied.  In  all  of  the  experiments  the  whipped 
blood  from  the  same  animal  diluted  a  number  of  times  with  normal  saline 
solution  was  used.  The  pure  blood  appears  to  be  much  too  thick  for  this 
experiment,  as  it  is  difficult  to  inject  it  through  the  capillaries  (Exp.  116). 
In  case  a  large  quantity  of  blood  was  needed,  that  which  flowed  from  the  vein 
was  whipped  and  again  injected  into  the  artery. 

Microscopic  Examinatiox  of  the  Mesenteric  Circulation.    Rate  of 

Venous  Outflow. 

In  Experiments  113-118  the  vessels  of  the  mesentery  were  constantly 
examined  with  the  low  power  of  the  microscope,  and  similar  microscopical 
examinations  were  made  of  the  mesenteric  circulation  after  ligature  of  the 
superior  mesenteric  artery  in  the  living  animal.  Examinations  of  this  sort 
proved  to  be  difficult  for  obvious  reasons,  yet  the  impressions  obtained  from 
continuous  study  of  the  same  specimen  during  consecutive  hours  are  fairly 
definite. 

Our  apparatus  consisted  of  a  microscope  illuminated  by  electric  light  and 
completely  immersed  in  the  saline  solution  of  the  warm  bath  in  which  the 
intestine  and  mesentery  were  floated.  It  was  necessarv"  to  be  careful  in 
handling  the  mesentery  for  any  stretching  of  it  interfered  materially  with 
the  circulation.    Either  hyperaemia  or  infarction  followed  in  every  case. 

In  these  experiments  the  arteries  are  at  first  contracted,  but  they  soon 
dilate  as  the  blood  shoots  through  them.  At  first  the  red  corpuscles  barely 
touch  one  another  as  they  flow  through  the  capillaries,  but  as  they  reach  the 
smaller  veins  there  is  a  tendency  for  them  to  accumulate  in  clumps  which  are 
then  broken  up  and  carried  on  into  the  larger  veins.  This  clumping  is 
observed  only  here  and  there,  being  rapidly  broken  up  by  the  advancing 


HAEMORRHAGIC  INFARCTION  99 

column  of  blood,  but  it  <ifradually  appears  in  more  and  more  of  the  veins,  and 
in  some  it  becomes  permanent,  producing  an  evident  obstacle  to  the  forward 
movement  of  the  blood.  These  clumps  and  columns  of  red  blood  corpuscles 
in  the  veins  may  be  pushed  along  by  the  current  or  they  may  move  to  and  fro 
or  eventually  become  stationary.  Similar  phenomena  of  distention  with 
red  blood  corpuscles,  to  and  fro  movement  of  the  same  and  eventual  steusis 
can  also  be  observed  somewhat  later  in  the  capillaries.  An  interesting 
appearance,  often  observed  in  the  veins  and  capillaries,  is  that  of  interrupted 
columns  of  compacted  red  blood  corpuscles  with  intervening  clear  spaces 
which  are  sometimes  clumps  of  white  corpuscles,  sometimes  of  platelets, 
sometimes  only  clear  plasma. 

Coincident  with  this  partial  blocking  of  the  veins  and  capillaries,  red 
blood  corpuscles  begin  to  pass  through  the  walls  of  these  vessels  by  diape- 
desis ;  and  after  a  time  the  haemorrhage  becomes  so  great  that  it  is  difficult 
to  observe  the  conditions  within  the  vessels.  The  venous  outflow  is  dimin- 
ished immediately  or  shortly  after  the  beginning  of  the  experiment,  it  then 
rises,  but  later  on  it  continuously  falls  to  a  minimum. 

Fig.  10  gives  the  pressure  curve  and  the  venous  outflow  of  Experiment  118. 
After  the  experiment  was  well  under  way  the  blood  elements  were  easily 
seen  in  the  arterioles,  capillaries  and  small  veins.  The  branching  of  the 
artery  appeared  to  be  the  cause  of  an  equal  distribution  of  the  corpuscles 
within  the  capillaries.  Frequently  the  red  discs  stuck  together,  but  these 
clumps  were  shattered  as  the  stream  of  blood  broke  to  enter  the  branches  of 
the  artery.  Throughout  the  capillaries  the  red  corpuscles  were  well  sepa- 
rated, but  as  they  entered  the  small  veins  the  corpuscles  again  began  to  form 
into  clumps.  These  clumps  of  corpuscles  were  nearly  always  headed  by 
hyaline  masses  apparently  composed  of  blood  platelets.  So  long  as  a  clump 
of  blood  corpuscles  met  no  obstacles  on  its  way  to  a  larger  vein  nothing 
happened,  but  as  soon  as  a  clump  met  another  clump  as  the  venous  bed 
became  smaller,  a  complete  obliteration  of  a  main  branch  followed.  Fre- 
quently pictures,  as  showTi  in  Fig.  11,  were  seen — columns  of  blood  headed 
by  hyaline  masses  would  come  against,  but  not  enter,  a  venous  stream,  h, 
which  remained  unbroken.  It  seemed  as  if  the  force  back  of  the  column,  a, 
was  not  strong  enough  to  drive  it  into  the  main  current,  h,  which  was  very 
rapid.  Increasing  the  arterial  pressure  forced  column,  c,  to  enter  the  main 
stream  but  it  was  extremely  difficult  to  dislodge  the  column,  a.  After 
raising  the  arterial  pressure  several  times  to  70  mm.  Hg.  the  column, 
a,  began  to  vibrate,  then  to  advance  slowly  and  finally  it  shot  into  the  main 
stream.  After  the  experiment  had  continued  for  two  hours  nearly  all  the 
veins  were  blocked,  but  raising  the  arterial  pressure  removed  the  obstruction. 
During  the  fourth  and  fifth  hours  (Fig.  10)  obstruction  due  to  the  forma- 


100  EXPERIMENTAL  STUDY  OF 

tion  of  clumps  in  the  veins,  took  place  a  second  time.  Each  time  this  condi- 
tion accompanied  low  arterial  pressure,  and  it  was  followed  by  a  diminished 
venous  outflow  and  an  intense  hyperaemia  of  the  intestine. 

In  Experiment  119  the  arterial  and  venous  pressure  were  kept  constant 
during  its  entire  duration,  but  the  venous  outflow  varied  greatly,  as  shown 
in  Fig.  12.  The  intestine  was  handled  very  little  in  observing  the  capillary 
circulation  with  the  microscope. 

Throughout  the  experiment  there  was  but  slight  tendency  for  the  cor- 
puscles to  form  in  clumps  and  no  infarction  followed.  During  the  third 
hour  there  was  a  marked  dilatation  of  the  veins  and  an  increased  outflow  of 
blood.  At  this  time  the  lymphatic  channels  of  the  mesentery  carried  off  a 
great  deal  of  lymph  in  which  there  w^as  a  considerable  number  of  red  blood 
corpuscles. 

The  record  of  Experiment  120  is  given  in  Fig.  13.  The  high  arterial 
pressure  at  the  beginning  and  again  at  the  end  of  the  experiment  need  not  be 
taken  into  consideration  for  the  intervening  four  hours  can  be  considered 
alone.  Again  we  had  the  curve  of  the  venous  outflow,  which  towards  the  end 
of  the  experiment  gradually  fell  nearly  to  zero.  At  this  time  the  infarction 
of  the  mucosa  was  complete  and  the  second  rise  of  arterial  pressure  caused  it 
to  intensify  greatly. 

Experiments  121  and  122  were  made  upon  the  intestine  of  dogs  of  the 
same  size  and  under  like  conditions  at  the  same  time,  differing  only  in  that 
the  arterial  pressure  in  one  was  high  and  in  the  other  low.  Fig.  14  gives  the 
curves  of  Experiment  121.  The  outflow  curve  is  the  usual  one.  There  was 
no  infarction  of  the  mucosa,  it  was  only  hyperaemic. 

The  arterial  pressure  of  Experiment  122  was  changed  several  times  in 
order  to  reduce  the  venous  outflow  to  the  lowest  possible  amount.  During 
the  whole  experiment  500  c.  c.  of  blood  entered  the  artery  and  but  116  c.  c. 
came  from  the  vein.  The  rest  was  used  in  the  production  of  the  infarction 
which  followed. 

The  whipped  blood  and  the  intestines  used  in  making  Experiments  123  and 
124  were  first  placed  in  the  ice  box  for  48  hours,  then  placed  in  the  warm 
chamber  and  artificial  circulation  carried  on  through  one  of  them  at  65  mm. 
and  the  other  at  20  mm.  Hg.  The  outflow  curve  of  123  is  given  in  Fig.  15; 
no  blood  came  from  tlie  vein  in  124.  In  these  two  experiments  the  conditions 
wpre  entirely  mechanical  as  the  int^^stine  as  well  as  the  blood  was  dead.  With 
the  low  pressure  infarction  followed,  while  with  the  high  pressure  the  mucosa 
was  only  hyperaemic  at  the  end  of  the  experiment. 

CONPITIONS  FOR  PRODUCTION  OF  HaEMORRHAGIC   INFARCTION 

The  expcrinicnt.«  given  in  Table  XIV  prove  that  haemorrhagic  infarction 
is  produced  in  the  isolated  intestine  under  conditions  similar  to  those  under 


HAEMORRHAGIC  INFARCTION  101 

which  it  occurs  within  the  living  body.  Moreover  whipped  blood  appears  to 
hasten  the  infarction.  The  amount  of  blood  which  flows  from  the  veins  when 
the  pressure  is  constant,  sometimes  after  a  transitory  diminution,  increases 
during  the  first  hour  of  the  experiment  then  gradually  diminishes.  The  first 
or  the  first  and  second  variations  of  the  venous  outflow  seems  to  run  parallel 
with  the  activity  of  the  contractions  of  the  muscular  walls  of  the  intestine. 
Similar  curves  have  been  demonstrated  by  Mosso  in  other  organs  either  alive 
or  dead  through  which  circulation  is  carried  on  with  whipped  blood  or  with 
blood  serum. 

The  cause  of  the  final  diminution  of  the  venous  outflow,  while  the  intes- 
tinal mucosa  is  becoming  hyperaemic  and  infarcted,  is  to  be  sought  within 
the  blood  current  due  to  the  absence  of  a  pulse  wave  as  already  demon- 
strated by  von  Frey.  Von  Frey  made  the  discovery  that  if  artificial  circula- 
tion is  carried  on  through  an  organ  ^dth  an  intermittent  pressure  imitating 
the  normal  pulse,  the  venous  outflow  equals  the  arterial  inflow.  When,  how- 
ever, the  arterial  pressure  is  constant  the  venous  outflow  diminishes,  due 
partly  to  contraction  of  the  capillary  walls  and  partly  to  a  remarkable  clog- 
ging of  the  capillaries  with  red  blood  corpuscles,  as  we  have  found  in  our 
experiments.  According  to  von  Frey  a  red  corpuscle  is  first  caught  at  the 
junction  of  two  capillaries,  partly  obstructs  their  lumina,  thus  acting  as  a 
filter  which  catches  up  more  red  corpuscles  which  finally  cause  complete 
obstruction.  A  pulsating  arterial  pressure  will  easily  dislodge  the  first  cor- 
puscle and  thus  keep  the  capillary  stream  open. 

In  our  experiments  we  found  that  the  first  obstruction  began  by  clumps 
of  corpuscles  lodging  in  small  veins,  but  we  were  unable  to  determine  whether 
these  are  first  formed  in  the  capillaries,  as  described  by  von  Frey,  then  be- 
come dislodged,  to  be  carried  on  into  the  smaller  veins  and  in  turn  obstruct 
them.  In  the  intestine  the  sectional  area  of  the  capillaries  is  300  times  that 
of  the  main  arter}';  in  the  smallest  veins  it  falls  to  170,  and  in  the  main 
vein  to  4.  The  moving  column  of  blood  must  divide  at  least  50  million  times 
during  a  small  fraction  of  a  second  in  passing  from  the  main  arteries  to 
the  capillaries.  This  rapid  divison  and  subdivision  of  the  column  appears 
to  be  sufficient  to  keep  the  corpuscles  within  the  arterial  stream  from  sticking 
together.  But  when  the  capillaries  are  reached  we  have  a  stream  which  is 
composed  of  a  single  row  of  corpuscles  which  can  no  longer  be  divided,  and 
also  a  relatively  slow  circulation.  Everything  is  favorable  for  them  to  cling 
to  the  capillary  walls  at  their  points  of  division  as  described  by  von  Frey. 
If  the  clumps  here  formed  are  dislodged  they  must  at  once  enter  a  venous 
bed,  which  is  but  half  as  large  as  the  capillary  bed  and  which  further  on 
diminishes  in  section  area  very  rapidly,  the  speed  of  the  circulation  at  the 
same  time  increasing  in  the  inverse  ratio  of  the  area  of  the  venous  bed.  The 
clumps  already  started  in  the  capillaries  are  carried  to  the  small  veins  and 


102  EXPEEIMENTAL  STUDY  OF 

soon  obstruct  them,  and  this  in  turn  favors  further  obstruction  of  the  capil- 
laries, as  well  as  of  the  neighboring  veins  for  a  greater  quantity  of  blood 
must  now  pass  through  them.  Finally  the  rapidity  of  the  capillary  circula- 
tion is  greatly  diminished  and  the  arterial  blood  pressure  is  now  extended  in 
greater  part  than  before  to  the  capillaries. 

It  is  evident  from  the  preceding  description  that  the  phenomena  observed 
under  these  peculiar  circulatory  conditions  are  in  large  part  dependent  upon 
the  physical  properties  of  the  blood  especially  upon  its  viscosity  and  the  pres- 
ence and  physical  characters  of  suspended  particles  which  readily  sticli 
together;  and  differ  in  important  respects  from  those  which  would  occur 
imder  similar  conditions  with  a  thin  homogeneous  fluid.  The  pressure 
gradient  from  the  arteries  to  the  veins  in  tlie  ischaemic  area  is  so  low  that 
the  red  blood  corpuscles  cannot  fully  overcome  the  resistance  in  the  veins 
and  capillaries.  They  accumulate  in  these  situations  and  probably  undergo 
some  physical  change  by  which  they  become  adherent  to  one  another  and  to 
the  vascular  wall.  The  absence  of  the  normal  pulse-waves  prevents  the 
breaking  up  of  these  masses  of  corpuscles,  the  long  pulse-waves  sometimes 
observed,  having  little  or  no  effect  in  distintegrating  the  masses.  In  this 
way  numerous  small  veins  and  capillaries  become  blocked,  with  the  resulting 
rise  of  intracapillary  pressure  and  diminution  of  outflow  of  blood  through 
the  veins. 

The  diapedesis  is  due  to  stagnation  of  the  blood,  and  to  blood  pressure. 
Without  a  certain  height  of  pressure  there  is  no  diapedesis ;  and  with  a  given 
retardation  and  stasis  of  blood-current,  the  higher  the  intracapillary  and 
intravenous  pressure  the  greater  the  amount  of  the  diapedesis.  The  matter 
which  needs  explanation  is  that  the  diapedesis  may  occur  with  lower  than 
normal  arterial  pressure,  and  through  vessels  walls  apparently  unaltered. 
This  we  attribute  to  the  fact  that  the  red  corpuscles,  in  consequence  of  the 
slow  circulation  and  absence  of  pulse-wave,  have  opportunity  to  become 
engaged  in  the  narrow  paths  followed  by  the  lymph  as  it  passes  between  the 
endothelial  cells.  Diapedesis  is  a  slow  process,  and  the  channels  for  it  are 
much  smaller  than  the  diameter  of  red  corpuscles.  Unless  the  red  cor- 
puscles can  get  started  on  the  path  between  the  endothelial  cells,  they  cannot 
traverse  it;  and  unless  the  circulation  is  very  much  slowed  and  the  out^r 
plasmatic  current  obliterated  there  is  no  opportunity  for  the  corpuscles  to 
become  engaged  between  the  endothelial  cells,  provided,  that  is,  the  vascular 
wall  is  normal.  With  greatly  retarded  circulation  there  is  this  opportunity 
and  when  the  way  in  front  is  blocked  by  compact  masses  of  red  corpuscles, 
and  sometimes  by  actual  agglutinative  thrombi,  the  only  path  open  for  the 
corpuscles  is  that  followed  by  the  lymph  between  the  endothelial  cells.  This, 
tben,  becomes  the  direction  of  the  least  resistance  for  their  movement. 


HAEMOREHAGIC  INFAECTION 


103 


Fig.  1. — Diagram  of  the  Superior  Mesenteric  Artery  and  Small  Intestine  to 
illustrate  Experiment  31.  Ligatures  were  applied  at  the  points  marked  X  The 
degree  of  shading  of  the  intestine  indicates  the  intensity  of  the  infarction  of  the 
mucosa.  The  numbers  opposite  the  convex  border  give  the  length  in  centimeters 
of  the  infarcted  zones.    The  letters  a,  a'  and  a"  refer  to  Experiment  12. 


25  cm 


Experiment  32 


Fig.   2. — Diagram  to  illustrate  Experiment  32.     X,  point  of  ligatures  of  the 
arteries  and  intestine.    The  infarction  is  marked  by  the  shaded  area. 


10-t 


EXPERIMENTAL  STUDY  OF 


35c 


Fio  3— Diagram  to  illustrate  Experiment  34.  X,  point  of  ligatures  of  the 
arteries  and  intestine.  The  zone  of  mucosa  3  cm.  long  is  oedematous.  the  zone 
10  cm.  long  is  infarcted  and  so  on. 


X 


_v: I 


X  X 


X 


H 


ZK. 


'C 


=^ 


"a^ 


)< 


:; 


f 


Normal  Hyperaemic  Infarcted 

Lxperimervt     3^ 
Fio.  4.— Scheme  of  vessels  of  Experiment  34.    A,  artery;  v,  vein;  c,  capillary. 


HAEMORRHAGIC  INFARCTION 


105 


Experiment  36  Exp.  37 

Fig.  5. — Diagram  of  Experiments  36,  37,  and 


Exp.  38 

X,  point  of  ligature. 


i 


Exp.  4  5 


X 


Exp.  40 


Exp.  4  3 


Exp.  46 


Exp.4I 


Exp.  4  4 


Exp.  47 


Fig.  6. — Diagram  of  Experiments  39  to  47.  The  artery  is  solid  and  the  vein 
outlined;  X,  point  of  ligature;  the  shading  indicates  the  intensity  of  the 
hyperaemia  or  the  infarction  of  the  mucosa. 


10 


106 


HAEMOREHAGIC  INFARCTION 


Experiment  48 

Fig.  7. — Diagram  of  Experiment  48. 


Experiment  49 
Fiu.  8. — Diagram  of  Experiment  49. 


Experimenis  66,  68  and  69. 
Fig.  9. — Diagram  of  Experiment  66.    X,  points  of  ligature;  arrow  shows  direc- 
tion of  the  circulation.     The  solid  vessel  represents  the  artery  and  the  outlined 
vessel  the  vein.    E,  point  artery  was  opened  in  Experiments  68  and  69. 


■mjn.  jsressure  ^nd 
C.C.  outflow 


Artery 


Venous  outflow 


Vefn 


o'clock 
jerimcnt  116 

Fig.  10. — Curve  of  Experiment  118.  The  broken  line  represents  the  arterial 
pressure;  the  dotted  line  the  venous  pressure;  the  unbroken  line  the  average 
outflow  in  c.  c.  for  5  minutes  reduced  5  times. 


Experinaent    118 


Fig.  11. — Tracing  of  a  small  vein  partly  blocked  with  clumped  red  corpuscles 
or  agglutinative  thrombi  from  Experiment  118. 


108 


EXPERIMENTAX.  vSTUDY  OF 


tnm.  pr«s»ur 
C  C.  outflow 


70 
60 
SO 
40  • 
30 
20  ■ 

to  - 

0 


.Artery 


...Outflow 


.Vein 


U  J  2  3  4  6   o'  clock 

Experiment    119 

Fig.  12. — Curve  of  Experiment  119.    The  outflow  curve  is  reduced  12  times. 


■mm.  pressure  aid 
cc.  outflow 


Artery 


Outflow 


o'clock 


Z  3  4 

Experiment    120 
Fio.  13. — Curve  ot  Experiment  120.    The  outflow  curve  is  reduced  10  times. 


HAEMOEEIIAGIC  INFAECTION 


109 


mm.  pressure  and 
C.C.  outflow 


90    ■ 
80 

TO 
60  4 
50 
^0 
30 
20 
10  f 
0 


Fig. 


Ouinow 


Artery 


-Vein 
o"*  clock 


Experiment  121 
14. — Curve  of  Experiment  121.     The  outflow  curve  is  reduced  6  times. 


Ynm. pressure  and 
cc.  outflow 


TO  ■ 

60  •• 
60    ■ 
40 
30 
20  [ 
10 


..    Arlery 


Out  fit 


Veirx 

o'clock 


Experiment  123 

Fig.  15. — Ourve  of  Experiment  123.     The  outflow  curve  is  reduced  6  times. 


THROMBOSIS ' 

Definition. — A  thrombus  is  usually  defined  as  a  blood-coagulum,  formed 
in  the  heart  or  vessels  during  life.  This  definition  applies  to  most  cases; 
but,  in  order  to  meet  the  objections  of  those  who  do  not  concede  that  all 
thrombi  are  genuine  coagula,  and  to  give  due  prominence  to  the  participation 
of  blood-platelets  and  corpuscles,  a  thrombus  may  be  more  broadly  defined 
as  a  solid  mass  or  plug  formed  in  the  living  heart  or  vessels  from  constituents 
of  blood.  Thrombosis  is  the  act  or  process  of  formation  of  a  thrombus,  or 
the  condition  characterised  by  its  presence. 

Structure  of  Tiiro:mbi. — The  formed  elements  which  may  enter  into 
the  composition  of  fresh  thrombi  are  blood-platelets,  fibrin,  leucocytes,  and 
red  corpuscles.  These  elements  may  be  present  in  varying  number,  propor- 
tion, and  arrangement,  whence  there  results  great  diversity  in  the  appearance 
and  structure  of  different  thrombi. 

The  two  main  anatomical  groups  of  thrombi  are  the  red  and  the  white 
thrombi.  Many  of  the  mixed  thrombi  may  be  regarded  as  a  variety  of  the 
white  thrombus.  In  addition  there  are  thrombi  of  relatively  minor  impor- 
tance composed  wholly  or  chiefly  of  leucocytes,  of  fibrillated  fibrin  or  of 
hyaline  material. 

Red  Thrombi. — These  are  formed  from  stagnating  blood,  and  in  the  recent 
state  do  not  differ  in  appearance  and  structure  from  clots  formed  in  shed 
blood.  They  are  made  up  of  fibrillated  fibrin  and  of  red  and  white  corpuscles 
in  the  same  proportions  as  in  the  circulating  blood,  or  the  white  corpuscles 
may  be  somewhat  in  excess.  If  any  part  of  such  a  red  thrombus  be  exposed 
to  circulating  blood,  white  material,  consisting  of  platelets  ^v^th  fibrin  and 
leucocytes,  is  deposited  upon  it.  This  deposit  may  aid  in  distinguishing 
the  thrombus  from  a  post-mortem  clot. 

White  and  Mixed  lliromhi. — Most  thrombi  are  formed  from  the  circulat- 
ing blood,  and  are  white,  or  of  a  mixed  red  and  white  colour.  The  white 
or  gray  colour  is  due  to  the  presence  of  platelefc*,  fibrin,  and  leucocytes,  occur- 
ring singly,  or,  more  frequently,  in  combination.  The  admixture  v^nth  red 
corpus(;lcs  is  not  an  essential  character  of  the  thrombus,  although  it  may 
be  sutficient  to  give  it  a  predominantly  red  colour. 

Fresh  white  human  thrombi,  when  examined  microscopically,  are  seen 
to  be  composed  of  a  granular  mat(Tial,  usually  in  islands  or  strands  of  vary- 

»In:    Syst.  Med.   (Allbutt),  Macmillan  Co.,  Lond.,  1899,  VII,  155-285. 
110 


THROMBOSIS  111 

ing  shape  and  size,  around  and  between  which  are  fibrin  and  leucocytes  with 
a  larger  or  smaller  number  of  entangled  red  corpuscles.  The  granular  mat- 
ter, to  which  the  older  observers  attached  comparatively  little  importance, 
and  which  they  interpreted  as  granular  or  molecular  fibrin  or  the  detritus  of 
white  corpuscles,  is  now  known  to  be  an  essential  constituent  of  the  white 
thrombus,  and  is  composed  chiefly  of  altered  blood-platelets.  Intact  polynu- 
clear  leucocytes  are  usually  numerous  in  the  margins  of  and  between  the 
masses  of  platelets,  and  may  be  scattered  among  the  individual  platelets. 
Not  less  important  is  the  fibrillated  fibrin,  which  is  generally  present  in 
large  amount.  It  is  particularly  dense  in  the  borders  of  the  platelet-masses, 
and  stretches  between  them  in  anastomosing  strands,  or  as  a  finer  network 
containing  red  and  white  corpuscles.  Within  the  accumulations  of  platelets 
in  fresh  thrombi  fibrin  is  often  absent,  or  is  in  small  amount.  These  various 
constituents  of  the  thrombus  often  present  a  definite  architectural  arrange- 
ment, and  soon  undergo  metamorphoses  which  \nll  be  described  subsequently. 

Thrombi  of  the  kind  just  described,  and  as  we  find  them  at  autopsies  on 
human  beings,  are  completed  products,  and  it  is  difficult,  indeed  generally 
impossible,  from  their  examination  to  come  to  any  conclusion  as  to  the 
exact  manner  of  their  formation;  particularly  as  regards  the  sequence  and 
relative  importance  of  their  different  constituents.  So  long  as  the  knowledge 
of  the  structure  of  thrombi  was  limited  to  that  derived  from  the  study  of 
these  completed  plugs,  the  coagulation  of  fibrin  was  generally  believed  to  be 
the  primary  and  essential  step  in  their  formation ;  although  A'irchow  pointed 
out  the  greater  richness  in  white  corpuscles  as  a  feature  distinguishing  them 
from  postmortem  clots. 

Zahn,  in  1872,  was  the  first  to  make  a  systematic  experimental  study, 
mainly  in  frogs,  of  the  mode  of  formation  of  thrombi.  He  came  to  the  con- 
clusion that  the  process  is  initiated  by  the  accumulation  of  white  corpuscles 
which,  by  their  disintegration,  give  rise  to  granular  detritus.  This  is 
quickly  followed  by  the  appearance  of  fibrin,  which  was  readily  accounted  for 
by  Weigert  on  the  basis  of  Alexander  Schmidt's  well-known  suggestion  of 
the  origin  of  fibrin  ferment  from  disintegrated  leucocytes.  Zahn's  views, 
anticipated  in  part  by  Mantegazza  in  1869,  and  confirmed  by  Pitres  in  1876, 
gained  prompt  and  wide  acceptance. 

Continued  experimental  study  of  the  subject,  however,  especially  upon 
mammals,  led  to  opposition  to  Zahn's  conclusions,  and  favoured  the  opinion, 
now  generally  accepted,  that  the  ordinary  white  thrombus  starts  as  an  accu- 
mulation not  of  leucocytes  but  of  blood-platelets.  The  investigators  chiefly 
concerned  in  the  establishment  of  this  doctrine  are  Osier  (1881-82),  Hayem 
(1882),  Bizzozero  (1882),  Lubnitzky  (1885),  and  Eberth  and  Schimmel- 
busch  (1885-86). 


112  THKOMBOSIS 

There  is  no  diflBculty  in  producing  thrombi  experimentelly  by  injury, 
either  mechanical  or  chemical,  to  the  vessel-wall ;  or  by  the  introduction  of 
foreign  bodies  into  the  circulation.  If  the  early  formation  of  such  a  thrombus 
be  observed  under  the  microscope  in  the  living  mesenteric  vessels  of  a  dog,  as 
was  done  by  Eberth  and  Schimmelbusch,  it  is  seen  that  the  first  step  consists 
in  the  accumulation  of  blood-platelets  at  tlie  seat  of  injury.  These  plates,  in 
consequence  of  their  viscous  metamorphosis,  at  once  become  adherent  to 
each  other  and  to  the  wall  of  the  vessel,  and  thus  form  plugs  which  may 
be  subsequently  washed  away  into  the  circulation,  but  which  sometimes  so 
increase  in  size  as  to  obstruct  the  lumen  of  the  vessel  completely.  Eed  and 
white  corpuscles  may  be  included  in  the  mass  of  platelets ;  but  their  presence 
at  this  stage  is  purely  accidental;  they  are  not  to  be  regarded  as  essential 
constituents  of  the  thrombus  in  its  inception. 

The  microscopial  examination  of  young  experimental  thrombi  confirms 
the  results  of  these  direct  observations,  and  affords  information  as  to  their 
further  development.  To  obtain  a  clear  idea  of  this  development,  thrombi 
should  be  examined  at  intervals  of  minutes  from  their  beginning  to  those 
half  an  hour  old  or  older.  I  reported  the  results  of  such  an  experimental 
study  in  1887.  The  material  composing  the  youngest  thrombi  formed  from 
the  circulating  blood  appears  macroscopically  as  a  soft,  homogeneous,  gray, 
translucent  substance  of  viscid  consistence.  Microscopically  it  is  made  up 
chiefly  of  platelets,  which  are  seen  as  pale,  round,  or  somewhat  irregular 
bodies,  var}ing  in  size  but  averaging  about  one-quarter  the  diameter  of  a 
red  corpuscle. 

Leucocytes,  which  may  be  present  in  small  number  at  the  beginning, 
rapidly  increase  in  number,  and  within  the  first  fifteen  minutes  to  half  an 
hour  they  are  usually  in  such  abundance  that  at  this  stage  of  its  formation 
they  must  be  considered  an  essential  constituent  of  the  thrombus.  They 
tend  to  collect  at  the  margins  of  the  platelet-masses  and  between  them. 
These  leucocytes  are  nearly  all  j^olynuclear,  and  usually  present  no  evidence 
of  necrosis  or  disintegration. 

With  the  accumulation  of  leucocytes,  fibrillated  fibrin,  which  at  first  was 
absent,  makes  its  appearance;  being,  as  pointed  out  by  Hanau,  especially 
well  marked  and  dense  in  the  margins  of  the  masses  of  platelets.  Within 
these  masses  it  is  usually  absent.  The  rapidity  with  which  leucocytes  and 
fibrin  are  added  to  the  masses  of  platelets  varies  much  in  different  cases.  At 
the  end  of  half  an  hour  the  thrombus  may  be  composed  of  platelets,  leuco- 
cytes, and  fibrin  with  entangled  red  corpuscles,  in  essentially  the  same  pro- 
portions and  with  the  same  arrangement  as  in  the  human  thrombi  already 
described ;  or  even  after  several  hours  it  may  still  consist  almost  wholly  of 
platelets. 


THROMBOSIS  113 

The  prevailing  view  is  that  platelets  exist  in  Dormal  blood,  where  they 
circulate  with  the  red  corpuscles  in  tlie  axial  current.  In  accordance  with 
this  view,  many  observers,  following  Eberth  and  Schimmelbusch,  explain 
the  beginning  of  a  white  thrombus  by  the  accumulation  of  pre-existing 
platelets  upon  a  foreign  body,  or,  in  consequence  of  slowing  or  other  irregu- 
larities of  the  blood-flow,  on  the  damaged  inner  wall  of  the  heart  or  vessels. 
Contact  with  the  abnomial  surface  sets  up  an  immediate  viscous  metamor- 
phosis of  the  platelets,  whereby  they  adbere  to  each  other  and  to  the  foreign 
body  or  vascular  wall.  Eberth  and  Schimmelbusch  designate  this  process 
as  conglutination,  and  distinguish  it  sharply  from  coagulation,  which  they 
regard  as  a  later  event  in  the  development  of  the  thrombus. 

Those  who  hold  with  Lowat,  tliat  platelets  do  not  exist  in  normal  blood, 
believe  that  they  are  produced  at  the  moment  of  formation  of  the  thrombus, 
as  the  result  of  injury  to  the  blood ;  and  many  who  believe  that  they  are  in 
normal  blood  not  as  independent  elements,  but  as  derivatives  from  leuco- 
cytes or  red  corpuscles,  consider  it  probable  that  those  in  the  thrombus  are 
formed,  at  least  in  part,  in  consequence  of  such  injury.  Although  there  are 
observations  which  suggest  that  platelets  may  be  derived  from  leucocytes, 
there  is  no  evidence  that  the  masses  of  platelets  found  in  incipient  thrombi 
come  from  leucocytes  previously  attracted  to  the  spot. 

Strong  evidence  has  been  recently  presented,  by  Arnold,  F.  Miiller,  and 
Determann,  in  favour  of  the  origin  of  platelets  from  red  corpuscles.  Wlassow, 
working  in  Ziegler's  laboratory,  finds  that  the  white  thrombus  is  formed 
primarily  by  the  destruction  of  red  corpuscles,  and  is  composed  at  the  very 
beginning  of  shadows  of  red  corpuscles,  corpuscular  fragments  both  with 
and  without  hemoglobin,  granular  material  and  pla.telets  of  nucleo-proteid 
substance;  all  derived  from  disintegrating  red  corpuscles.  A  similar  view 
is  entertained  by  Mosso,  Klebs,  Arnold,  Ziegler,  and  F.  Miiller. 

The  accumulation  of  leucocytes  in  the  young  thrombus  may  be  explained 
partly  by  mechanical  causes, — tJie  most  evident  being  the  projecting,  irregu- 
lar, sticky  substance  of  the  platelet  masses  associated  with  slowing  and  eddies 
of  the  blood-stream, — and  partly  by  chemiotactic  influences. 

Whatever  difficulties  there  may  be,  in  accounting  for  tlie  fibrin,  relate  to 
the  general  subject  of  coagulation  of  the  blood  (see  Professor  Foster's  article 
in  Allbutt's  "  System  of  Medicine,"  VI,  p.  403 )  rather  than  to  the  special 
conditions  of  the  thrombus.  As  to  the  participation  of  platelets  in  the  pro- 
duction of  fibrin,  opinion  is  divided;  and  upon  this  point  the  study  of 
thrombi  has  not  afi^orded  conclusive  evidence  one  way  or  the  other.  The 
usual  absence  of  fibrin  within  the  platelet  masses  for  a  considerable  time 
after  their  formation  may  be  tliought  to  speak  against  the  generation  of 
fibrin-ferment  by  the  platelets.    But  if,  as  is  probable,  the  platelets  contain 


114  THKOMBOSIS 

nueleo-proteid,  it  would  be  rea^sonable  to  suppose,  in  accordance  with  cur- 
rent physiological  ideas,  that  they  can  yield  one  of  the  fibrin  factors ;  and  it 
may  be  that  in  these  compact  masses  there  is  not  enough  fibrinogen  furnished 
by  the  plasma  to  generate  an  appreciable  amount  of  fibrin.  The  character- 
istic dense  ring  of  fibrin  immediately  around  the  platelet  masses,  where  there 
is  abundant  fibrinogen,  could  be  interpreted  in  favour  of  the  liberation  of 
fibrin-ferment  by  the  collected  platelets.  By  the  time,  however,  that  the 
fibrin  appears,  leucocytes  have  also  accumulated  in  the  same  situation ;  and 
they,  either  alone  or  together  with  the  platelets,  may  be  the  source  of  the 
ferment;  although,  as  already  stated,  the  leucocytes  in  young  thrombi  gener- 
ally show  apparently  intact  nuclei  and  cytoplasm. 

Does  the  recognition  of  the  described  mode  of  development  of  a  white 
thrombus  necessitate  a  radical  break,  such  as  that  made  by  Eberth  and  Schim- 
melbusch,  with  the  old  and  still  common  conception  that  a  thrombus  is 
essentially  a  blood  coagulum?  This  question  applies  only  to  the  first  stage 
of  formation  of  a  white  thrombus,  for  the  completed  thrombus  is  undoubtely 
a  coagulum.  It  is,  however,  of  both  scientific  and  practical  interest  to  inquire 
whether  coagulative  phenomena  usher  in  the  process  of  thrombosis  or  are 
merely  secondary'.  A  decisive  answer  to  this  question  cannot  be  given  until 
we  are  better  informed  than  at  present  concerning  the  chemistry  and 
morphology  of  coagulative  processes,  and  the  source  and  properties  of  the 
granular  material  constituting  the  youngest  thrombi.  The  possibility  that 
this  material  is  already  coagulated;  and  falls  into  the  category'  of  the  coagu- 
lative necroses,  has  been  suggested  by  Weigert;  but  without  any  proof  of  this 
view.  There  is  greater  probability  that  the  accimiulation  and  metamorphoses 
of  the  so-called  platelets  in  beginning  thrombi  represent  a  preparation  for 
coagulation  or  a  first  step  in  the  process.  As  Hammerstcn  has  pointed  out, 
two  chemical  phases  are  to  be  distinguished  in  the  process  of  coagulation; 
namely,  the  formation  of  fibrin  ferment  from  its  zymogen,  and  the  transfor- 
mation of  fibrinogen  into  fibrin  under  the  influence  of  this  ferment.  Morph- 
ological phases  may  also  be  distinguished,  and  the  platelet  stage  of  thrombus 
formation  may  bo  interpreted  as  the  first  morphological  phase  of  coagulation 
in  circulating  blood.  According  to  Whissow  a  similar  morphological  phase 
may  be  recognised  in  the  clotting  produced  by  whipping  shed  blood.  It  would 
lead  too  far  afield  to  enter  bore  into  a  discussion  of  the  arguments  in  favor 
of  this  view;  but  much  in  it>^  support  is  found  in  recent  chemical  and  mor- 
phological studies  of  extra  vascular  and  intravascular  coagulation,  and  of  the 
anatomical  and  cliemical  characters  of  blood  platelets.*    It  does  not  appear, 

'  This  recent  work  has  been  critically  reviewed  by  Lowit  in  Lubarsch-Ostertag's 
Ergebnisse,  1897. 


THROMBOSIS  115 

therefore,  that  we  are  called  upon  at  present  to  make  any  such  radical 
revision  of  the  traditional  conception  of  white  thrombi  as  coagula,  as  has 
been  advocated  of  late  years  by  some  writers, 

Leucocytic  Thrombi. — As  has  already  been  explained,  leucocytes,  although 
they  do  not  usher  in  the  process  of  ordinary  throm])osis,  make  their  appear- 
ance at  an  early  stage,  and  other  accumulate  in  sucli  numbers  as  to  consti- 
tute a  large  part  of  the  tlirombus.  My  studies  of  experimental  and  human 
thrombi  have  led  me  to  assign  to  tliem  a  more  important  part  in  the  con- 
struction of  white  thrombi  than  that  indicated  by  Eberth  and  Schimmel- 
busch.  Whether  the  regular  mural  white- thrombi  ever  arise  as  a  collection 
of  leucocytes,  in  the  manner  described  by  Zalin,  is  uncertain.  Such  a  mode 
of  development,  if  it  occurs,  is,  I  think,  exceptional.  Intravascular  plugs, 
however,  occur,  which  are  made  up  wholly  or  predominantly  of  polynuclear 
leucocytes.  These  are  found  mainly  in  small  vessels  in  acutely  inflamed 
regions,  where  they  are  to  be  regarded  as  inflammatory  and  prol^ably  chemi- 
otactic  in  origin.  Leucocytic  masses  may  also  be  found  after  death  in  small 
vessels  in  leucocytha^mia,  and  in  diseases  with  marked  leucoeytosis ;  but  it  is 
probable  that  these  are  not  genuine  obstructing  plugs. 

Purely  Fibrinous  Thrombi. — As  will  be  described  subsequently,  fibrin 
usually  increases  in  amount  with  the  age  of  the  thrombus.  The  masses  of 
platelets  may  be  replaced  by  fibrin,  and  leucocytes  may  degenerate ;  so  that 
many  old,  unorganised  thrombi  consist  of  practically  nothing  but  dense 
fii)rin,  in  places  hyaline.  I  do  not,  however,  desire  now  to  call  especial 
attention  to  these  old,  metamorphosed  thrombi. 

One  sometimes  finds  in  inflamed  areas,  less  frequently  under  other 
circumstaaices,  the  vessels,  particularly  those  of  small  size,  partly  or  com- 
pletely filled  with  fibrillated  fibrin,  presenting  such  an  arrangement  and 
configuration  as  to  indicate  coagulation  during  life.  Neither  leucocytes 
nor  platelets  need  take  part  in. the  formation  of  these  plugs  of  pure  fibrin, 
although  sometimes  they  are  present.  K.  Zenker  has  well  described  the 
microscopical  appearances  in  these  cases.  Whorls  or  brush-like  clumps  of 
fibrin  may  spring  at  intervals  from  the  wall  of  the  vessel,  where  tliey  are 
attached  especially  to  necrotic  endothelium  or  to  points  devoid  of  endothe- 
lium. The  fibrin  may  be  disposed  regularly,  often  in  stellate  figures,  around 
definite  centres  in  which,  perhaps,  a  necrotic  cell  or  fragment,  endothelial  or 
leucocytic,  or  a  climip  of  platelets  can  be  demonstrated.  The  fibrin  is  often 
notably  coarse.  The  affected  vessels  are  not  usually  filled  completely  ^vitll 
fibrin,  and  they  can  be  artificially  injected.  In  croupous  pneumonia  such 
fibrinous  masses  are  regularly  present,  both  in  capillaries  and  larger  vessels 
of  the  hepatised  area.  These  purely  fibrinous  coagula  are  of  anatomical 
rather  than  clinical  interest. 


116  THROMBOSIS 

Hyaline  Thrombi. — These  are  of  more  interest  and  importance  than  the 
purely  fibrinous  and  leucocytic  thrombi  just  described.  The  presence  of  hya- 
line material  in  old  white  thrombi  will  be  spoken  of  subsequently.  To  von 
Recklinghausen  we  especially  owe  the  recognition  of  hyaline  thrombi  as  a 
distinct  class.  They  are  found  especially  in  the  capillaries,  but  may  occur 
also  in  the  smaller  arteries  and  veins.  The  capillaries  are  filled  with  a 
refractive,  homogeneous,  translucent,  colourless  or  faintly  yellow  material, 
which  stains  well  with  Weigert's  fibrin  dye.  The  same  material  may  partly 
or  completely  fill  the  smaller  arteries  and  veins.  Balls,  as  well  as  cylindrical 
masses,  of  this  hyaline  substance  may  be  found,  especially  in  tlie  cerebral 
vessels. 

This  hyaline  thrombosis  has  been  observed  in  a  variety  of  conditions, 
partly  general,  partly  local.  It  occurs  especially  in  infective  and  toxic 
diseases.  Kriege  found  extensive  hyaline  thrombosis  in  the  small  vessels 
after  freezing  the  rabbit's  ear.  Yon  Recklinghausen  had  previously  attrib- 
uted to  this  cause  spontaneous  gangrene  of  both  feet  occurring  in  an  old 
woman  who  had  suffered  repeatedly  from  slight  frost-bites ;  and  he  likewise 
found  the  same  hyaline  vascular  plugs  in  cases  of  mortification  following 
experimental  ergotism.  Capillary  hyaline  thromboses  are  common  in  the 
lungs  in  pneumonia,  and  in  hjemorrhage  infarcts.  In  general  infective  and 
toxic  states  they  may  be  present  in  the  liver,  the  lungs,  and,  above  all,  in  the 
kidneys. 

The  most  striking  examples  of  this  form  of  thrombosis,  with  which  I 
am  acquainted,  are  encountered  in  the  renal  capillaries,  chiefly  of  the  glo- 
meruli, of  swine  dead  of  hog-cholera;  or  of  animals  infected  with  the  hog- 
cholera  bacillus.  In  extreme  cases  there  is  complete  anuria;  and  it  may  be 
impossible  to  force  more  tlian  a  minimal  amount  of  injecting  fluid  into 
the  renal  vessels.  Sections  stained  with  Weigert's  fibrin-stain  look  as  if 
the  capillaries  had  been  injected  with  Berlin  blue.  Ribbert  found  similar 
hyaline  thrombi  in  the  kidneys  of  rabbits  inoculated  with  S.  pyogenes 
aureus.  I  have  repeatedly  found  them  in  various  experimental  infections, 
and  in  human  infections.  They  occur  in  eclampsia.  Bacteria  are  not  neces- 
sarily present,  so  that  toxins  are  probably  the  underlying  causative  factor, 
and  for  this  there  is  experimental  evidence. 

Klebs  and  others  have  thought  that  the  hyaline  material  is  derived  from 
coalesced  and  altered  red  corpuscles.  Red  corpuscles  may  in  fact  be  so 
crowded  together,  and  apparently  coalesced,  as  to  appear  as  nearly  homo- 
geneous yellowish  cylinders  (globular  stasis).  The  genuine  hyaline  thrombi 
have  the  staining  reactions  of  fibrin,  and  are  often  continuous  with  ordinary 
fibrillated  fibrin  in  larger  vessels.  Transitions  between  fibrillated  fibrin 
and  the  hyaline  material  can  sometimes  be  seen ;  but  it  is  often  impossible 


THROMBOSIS  117 

by  any  staining  to  resolve  the  latter  into  a  fibrinous  network.  If  the  recent 
views  previously  mentioned  concerning  the  origin  of  platelets  from  red  cor- 
puscles and  the  participation  of  these  corpuscles  in  the  process  of  coagula- 
tion be  accepted,  there  would  be  no  difficulty  in  adopting  Klebs's  hypothesis 
as  to  the  origin  of  hyaline  thrombi  from  red  corpuscles.  Von  Reckling- 
hausen and  Kriege  find  evidence  that  the  hyaline  substance  is  derived  from 
leucocytes. 

Growth,  Metamorphoses,  and  Organisation  of  Thrombi. — Thrombi 
in  their  growth  assume  various  characters  to  which  special  epithets  are 
applied.  A  thrombus  formed  from  the  circulating  blood  is  at  first  parietal 
or  mural,  but  by  continued  growth  it  may  fill  the  vessel  and  become  an 
occluding  or  obstructing  thrombus.  A  primitive  or  autochthonous  thrombus, 
caused  by  local  conditions,  may  be  the  starting-point  of  a  continued  or 
propagated  thrombus,  extending  in  the  course  of  the  thrombosed  vessel  and 
perhaps  into  communicating  vessels.  A  secondary  or  encapsulating  throm- 
bus is  one  which  starts  from  an  embolus  of  thrombotic  material.  A  con- 
tinued thrombus  is  also  often  spoken  of  as  secondary.  Thrombi  are,  with 
rare  exceptions,  adherent,  at  least  in  places,  to  the  wall  of  the  vessel  or 
the  heart.  Mural  thrombi  appear  more  or  less  flattened  against  the  vessel- 
wall,  or  they  may  project  in  a  globular  or  polypoid  form  into  the  lumen. 
Their  free  surface  is  generally  rough.  Loose  thrombi  in  the  heart  are  called 
ball- thrombi. 

The  thrombus  grows  in  length  chiefly  in  the  direction  of  the  current  of 
blood ;  but  it  may  grow  in  the  opposite  direction.  The  intact  and  growing 
end  of  the  thrombus  is  a  flattened  blunt  cone  usually  not  adherent  to  the 
wall  of  the  vessel;  it  is  sometimes  compared  in  shape  to  a  serpent's  head. 
A  venous  thrombus  extends  in  the  direction  of  the  circulating  blood,  not  only 
as  far  as  the  next  branch,  but  frequently  a  greater  or  less  distance  beyond 
it,  in  the  form  of  a  mural  thrombus.  A  thrombus  is  at  first  soft  in  consis- 
tence and  moist ;  but  by  contraction  and  extrusion  of  fiuid  it  becomes  more 
compact,  firmer,  drier,  and  more  granular  in  texture. 

Mural  thrombi,  especially  small  ones,  such  as  fresh  vegetations  on  the  car- 
diac valves,  may  occur  without  any  definite  arrangement  of  the  constituent 
elements.  Such  thrombi  may  consist  almost  wholly  of  platelets;  but  it  is 
most  exceptional  not  to  find  at  least  some  admixture  with  leucocytes  and 
fibrin  coagulated  intra  vitam. 

The  larger  white  and  mixed  thrombi  often  present  a  typical  architecture. 
The  stratified  structure  has  long  been  known  and  emphasised.  More  recently 
Zahn  has  directed  especial  attention  to  the  rib-like  markings  on  the  free 


118  THROMBOSIS 

surfaces.'  and  Asclioft'  to  tlie  internal  ardiiteeturc  of  white  and  mixed 
thrombi.  Microscopical  sections  of  these  thrombi  often  show  an  exquisitely 
trabecular  structure  due  to  irretpilarly  contoure<l,  anastomosino;  columns  and 
lamelhv,  of  varying  size  and  shape,  which  spring  at  intervals  from  the  wall 
of  the  vessel  and  extend,  usually  in  an  oblique  or  twisting  direction,  toward 
tlie  free  surface  of  the  thrombus,  upon  which  their  extremities  from  the 
network  of  whitish  lines  or  the  transverse  ribs  noted  by  Zahn.  If  the  throm- 
bus be  detached  from  the  inner  wall  of  the  vessel,  similar  projecting  lines  and 
dots  can  be  seen  on  its  attaclied  surface  and  often  on  the  inner  lining  of 
tlie  vessel.  This  trabecular  framework  of  the  thrombus  is  composed  of 
masses  of  platelets  with  cortical  layers  of  fibrin  and  leucocytes,  as  already 
described.  The  whole  arrangement  is  aj)tly  compared  by  Aschoff  to  branch- 
ing coral  stems.  The  spaces  between  the  trabecular  contain  blood  wliicli 
during  life  may  be  fluid  or  may  have  coagulated;  or  they  may  contain  only 
fibrin  and  leucocytes,  or  an  indefinite  mixture  of  platelets,  fibrin  and  red 
and  white  corpuscles.  Between  the  lanuiUe  and  columns  bands  of  fibrin 
with  or  without  platelets,  often  stretch  loosely  and  in  a  curved  manner,  the 
concavity  of  the  curve  looking  toward  the  axis  of  the  vessel.  AschofT  explains 
the  coral-like  architecture  and  the  ribbed  surface  of  the  tlirombus  partly 
by  the  oscillatory  or  wave-like  motion  of  the  flowing  blood,  w^iich,  as  pre- 
viously suggested  by  Zahn,  may  account  for  the  ribs,  and  partly  by  slight 
irregularities  of  surface  level  normally  present  in  the  inner  lining  of  vessels. 
Zahn  finds  an  analogy  between  the  ribs  of  a  thrombus  and  the  ripple-marks 
in  sand  at  the  edge  of  the  sea,  or  at  the  bottom  of  flowing  streams.  Before 
Zahn,  Wickham  Lcgg,  in  1878,  described  the  surface  of  a  cardiac  tlirombus 
as  "  marked  by  lines  resembling  the  impressions  made  by  the  waves  on  a 
sandy  shore." 

The  usual  explanation  of  the  red  and  white  stratification  of  mixed  thrombi 
is  that  the  tlirombus  is  deposited  in  successive  layers,  of  which  the  red  are 
formed  rapidly  and  the  white  more  slowly.  There  are  manifest  difficulties 
in  such  an  explanation.  It  is  more  probable  that  the  red  layers  are  cruor 
clots  formed  from  blood  brought  to  a  standstill.  Blood  entering  crevices, 
spaces,  and  clefts  resulting  from  the  irregular  mode  of  growth  of  the  throm- 
bus, or  from  its  contraction,  or  from  the  blood-stream,  often  with  increase 
of  pressure  in  consequence  of  the  thrombotic  barrier,  undermining  and  split- 
ting the  white  substance,  at  first  soft  and  later  brittle,  of  the  thrombus,  may 
readily  stagnate  and  clot.     Indications  of  such  a  splitting  of  the  thrombus 

^  A  number  of  writers  before  Zahn  observed  the  markings  on  the  surfaces  of 
thrombi.  Brlstowe  in  1855  spoke  of  the  "  peculiar  ribbed  appearance  "  of  the 
surface  of  cardiac  thrombi  (Trans.  Path.  Soc.  London,  VII,  p.  141). 


THROMBOSIS  119 

by  the  circulating  blood  are  often  seen  in  horizontal  white  lamellae  covering 
red  layers  and  present  within  them :  these  lamella  are  apparently  split  off 
from  the  general  framework  and  bent  in  the  direction  of  the  blood-current. 
The  typical  architecture  of  the  thrombus  may  not  appear,  or  may  be 
obscured  or  destroyed  by  displacement  of  its  parts  through  the  blood-stream, 
especiall}'  when  this  is  forcible:  hence  it  is  often  missed  in  arterial  thrombi. 
White  thrombi  are,  as  a  rule,  microscopically  mixed  thrombi ;  and  in  colour 
there  is  every  transition  from  these  to  thrombi  so  red  that  careful  examina- 
tion is  required  for  tlie  detection  of  the  white  substance. 

In  long  propagated  venous  thrombi  smaller  white  thrombus-masses  often 
alternate  in  a  longitudinal  direction  with  longer  red  ones.  The  explanation 
of  tliis  is  that  a  primary  white  thrombus  is  formed,  often  starting  from  a 
valvular  pocket.  This  becomes  an  occluding  thrombus,  and  the  column  of 
blood  reaching  to  the  nearest  branch,  or  to  the  confluence  of  two  important 
veins,  is  brought  to  a  standstill,  and  forms  a  red,  obstructing  thrombus.  At 
the  extremity  of  this,  where  the  blood  enters  from  the  branch,  another  white 
occluding  thrombus  may  be  formed,  to  be  followed  again  by  a  red  thrombus, 
and  so  on.  Thrombi  are  sometimes  described  as  red  in  consequence  of  failure 
to  detect  the  small  white  autochthonous  part  of  the  thrombus.  In  fact  the 
term  mixed  thrombus  is  applied  to  three  different  appearances  of  thrombi : 
(a)  an  intimate  mixture  of  gray  and  red  substances;  (6)  stratification  in 
successive  gray  and  red  layers,  and  (c)  red  propagated  clots  consecutive  to 
autochthonous  white  or  mixed  thrombi. 

In  old  thrombi  various  metamorphoses  have  occurred  which  obscure  or 
obliterate  the  typical  structure  and  architecture  of  the  younger  ones.  The 
masses  of  platelets,  although  they  may  persist  a  long  time,  become  finely 
granular,  sometimes  almost  or  quite  homogeneous  in  texture.  They  are 
invaded  by  fibrin,  especially  along  the  edges  of  spaces  and  clefts  which 
appear.  Notwithstanding  these  profound  clianges  a  certain  configuration 
and  a  differentiation  in  staining  properties  often  enable  us  to  recognise  the 
sites  of  the  original  columns  and  lamellae  of  platelets.  The  leucocytes,  often 
at  an  early  date,  undergo  fatty  degeneration  and  necrosis,  their  nuclei  dis- 
appearing both  by  karyolysis  and  karyorrhexis.  The  leucocytic  detritus  adds 
to  the  granular  material  of  tlie  thrombus.  The  red  corpuscles  are  decolour- 
ised and  fragmented.  The  haemoglobin  is  in  part  dissolved  and,  after  organi- 
sation begins,  is  partly  transformed  into  amorphous  and  crystalline  haema- 
toidin.  These  pigmentary  transformations  impart  a  brownish  red  colour  to 
red  and  mixed  thrombi.  Fibrin  increases  in  amount  and  becomes  coarse  and 
dense.  The  part  of  the  thrombus  adjacent  to  the  vessel-wall  is  often  con- 
verted into  compact  concentric  layers  of  fibrin  at  a  period  when  masses  of 
platelets  are  well  preserved  nearer  the  lumen.    The  hyaline  material,  which 


120  THROMBOSIS 

is  very  frequently  found  in  layers  and  clumps  in  old  thrombi,  may  be  derived 
both  from  fibrin  and  from  platelets ;  perhaps  also  from  red  corpuscles  and 
leucocytes.  It  may  stain  well  by  Weigert's  fibrin-stain,  or  only  faintly,  or 
not  at  all.  Small  spaces  and  canals,  often  containing  nucleated  cells,  may 
be  present  in  the  homogenous  fibrin  or  hyaline  substance  (canalised  fibrin 
of  Langhans) . 

Of  special  importance  are  the  liquefactive  softenings  which  may  occur 
in  old  thrombi.  These  are  distinguished  as  simple  or  bland,  septic  or  puru- 
lent, and  putrid  softenings. 

The  simple  softenings  occur  in  bland  thrombi,  being  especially  common 
in  globular  cardiac  thrombi  which,  when  old,  regularly  contain  in  their 
interior  an  opaque  whitish  or  reddish  thick  fluid.  This  in  old  days  was  mis- 
taken for  pus,  and  hence  the  name  puriform  softening  (purulent  cysts). 
The  liquid  or  pulpy  material  is  the  result  of  granular  disintegration  and 
liquefaction  of  the  solid  constituents  of  the  thrombus,  and  consists  of  necro- 
tic fatty  leucocytes,  albuminous  and  fatty  granules,  blood  pigment  and 
altered  red  corpuscles ;  the  varying  red  tint  of  the  fluid  depending  upon 
the  number  of  red  corpuscles  originally  present  in  the  thrombus.  Occasion- 
ally acicular  crystals  of  fatty  acid  are  present.  This  form  of  softening  is 
probably  due  to  the  action  of  some  ferment;  it  occurs  in  ordinary  bland 
thrombi,  and  is  distinguished  from  the  infective  forms.  It  is  not  generally 
supposed  that  micro-organisms  are  in  any  way  concerned  in  the  process : 
bacteria,  however,  have  been  found  of  late  years  repeatedly  in  these  thrombi ; 
and  it  may  be  that  they  are  not  so  absolutely  unconcerned  in  simple  throm- 
botic softening  as  is  generally  thought  to  be  the  case. 

There  is  no  question  as  to  the  participation  of  bacteria  in  the  otiier  forms 
of  softening.  Septic  or  purulent  softening,  met  with  most  frequently  in 
infective  thrombo-phlebitis,  is  a  true  suppuration ;  being  the  result  of  tlie 
accumulation  of  polynuclear  leucocytes  with  fermentative  liquefaction  of 
the  thrombus.  The  leucocytes  are  attracted  in  part  from  the  blood  of  the 
tlirombosed  vessel  and  in  part  from  the  vasa  vasorum  and  surrounding 
capillaries  and  veins.  Pyogenetic  bacteria,  most  frequently  streptococci, 
are  present  in  the  thrombus  and  the  walls  of  the  vessel.  Putrid  softening 
is  due  to  the  invasion  of  putrefactive  bacteria.  Here  the  thrombus  is  of  a 
dirty  brown  or  green  colour,  and  of  foul  odour. 

These  various  softenings  often  lead  to  the  separation  of  tlirombotic  frag- 
ments to  be  transported  by  the  circulation  as  emboli, — bland,  septic,  or 
putrid  according  to  the  nature  of  the  process. 

White  thrombi  in  veins,  far  lass  frequently  in  arteries,  may  undergo  calci- 
fication, forming  phlelxjliths  or  arterioliths.  They  are  generally  approxi- 
mately spherical,  and  lie  loosely  or  slightly  adherent  in  the  lumen.     They 


THROMBOSIS  121 

are  found  most  frequently  in  the  vedns  around  the  prostate  and  bladder  of 
men,  in  the  plexus  pampiniformes  of  women,  and  in  the  spleen. 

One  of  the  most  interesting  adaptive  pathological  processes  is  the  so- 
called  organisation  of  thrombi,  which  is  the  substitution  for  the  thrombus 
of  vascularised  connective  tissue.  The  thrombus  itself  takes  no  active  part 
in  the  process,  but  behaves  as  a  foreign  body.  It  is  gradually  disintegrated 
and  absorbed,  largely  through  the  activities  of  phagocytes.  The  new  tissue 
springs  from  the  wall  of  the  vessel  or  ttie  heart;  the  tissue-forming  cells 
being  derived  both  from  the  endothelium  and  from  other  fixed  cells  in  the 
wall.  New  vessels  spring  from  the  vasa  vasorum.  Lacunar  spaces  in  the 
thrombus,  or  between  the  thrombus  and  tlie  vascular  wall,  may  become  lined 
witli  endothelium,  and  also  ser\'e  as  channels  for  the  circulating  blood.  These 
new  vessels  may  establish  communication  with  the  lumen  of  the  thrombosed 
vessel  above  or  below  the  thrombus,  or  on  both  sides.  The  new  tissue,  which 
at  first  is  rich  in  cells,  becomes  fibrous,  and  contracts.  The  result  may  be 
a  solid  fibrous  plug,  or  a  cavernous  structure  vrith  large  blood-spaces ;  or,  by 
disappearance  of  the  septa,  a  restoration  of  the  lumen,  with  perhaps  a  few 
fibrous  threads  or  bands  stretching  across  it,  as  in  the  normal  cerebral  venous 
sinuses. 

There  are  great  diversities  in  indiWdual  cases  as  to  the  rapidity  of  onset 
and  the  course  of  the  organising  process ;  these  differences  depending  upon 
various  circumstances,  the  most  important  of  which  are  the  location  of  the 
thrombus,  the  condition  of  the  wall  of  the  vessel  or  heart,  the  general  state 
of  the  patient,  and  the  presence  or  absence  of  infection.  In  favourable 
cases  the  process  may  be  well  under  way  within  a  week.  The  wall  of  the 
vessel,  or  of  the  heart,  may  be  so  diseased  as  to  be  incapable  of  furnishing 
any  new  tissue ;  as  is  usually  the  case  in  aneurysmal  sacs,  and  often  in  varices 
and  in  cardiac  disease.  The  presence  of  pyogenetic  bacteria  prevents  or 
delays  the  process  of  organisation.  The  process  is  a  proliferative  angeiitis. 
It  is  this  angeiitis  which  leads  to  the  closure  of  a  vessel  after  ligation.  If 
the  ligature  be  applied  aseptically,  and  without  injury  to  the  internal  coats, 
usually  no  thrombus  is  formed,  or  only  a  very  small  one.  The  formation 
of  a  thrombus  is  of  no  assistance  in  securing  obliteration  of  a  ligated  vessel, 
in  fact  it  impedes  the  development  of  the  obliterating  endarteritis. 

The  causes  of  organisation  of  throml)i  are  probably  to  be  sought  partly  in 
the  influence  exerted  by  the  thrombus  as  a  foreign  body,  and  partly  in  slow- 
ing or  cessation  of  the  blood-current  and  lowering  of  the  tension  of  the 
vessel-wall  (Thoma,  Beneke).  Whetlier,  in  addition,  growth  of  cells  may  be 
determined  by  chemical  substances  derived  from  the  thrombus  is  uncertain. 

Etiology. — The  recognition  of  the  three  classes  of  causes  assigned  for 
thrombosis,  namely,  alterations  in  the  blood,  mechanical  disturbances  of  the 
11 


122  THROMBOSIS 

circulation  ajid  lesions  of  the  vascular  or  cardiac  wall,  is  not  of  recent  date. 
The  dyscrastic  theory  is  the  oldest.  John  Hunter  introduced  and  Cruveil- 
hier  elaborated  the  conception  of  primary  phlebitis  with  consecutive  plugging 
of  the  vein ;  and  Baillie,  Laennec,  Davy  and  others  emphasised  stasis  as  a 
cause  of  intravascular  clotting.  Virchow's  name,  however,  is  the  one 
especially  associated  with  mechanical  explanations  of  thrombosis.  The 
experiments  of  Briicke,  showing  the  importance  of  integrity  of  the  vascular 
wall  in  keeping  the  blood  fluid,  led  to  general  recognition  of  the  part  taJien 
by  alterations  of  this  wall  in  the  etiology  of  thrombosis. 

While  it  is  generally  agreed  that  slowing  and  other  irregularities  of  the 
circulation,  contact  of  the  blood  with  abnormal  surfaces,  and  changes  in  the 
composition  of  the  blood  are  concerned,  singly  or  in  combination,  in  the 
causation  of  thrombosis,  there  is  much  difference  of  opinion  as  to  the  rela- 
tive importance  of  each  of  these  factors,  and  as  to  the  part  of  each  as  a  proxi- 
mate, as  a  remote,  or  as  an  accessory  cause. 

Slowing  and  Oilier  Irregularities  of  the  Circulation. — Diminished  velocity 
of  the  blood-current  is  not  by  itself  an  efficient  cause  of  thrombosis.  The 
circulation  may  be  at  a  low  ebb  for  a  long  time  without  tlie  occurrence  of 
thrombi.  A  stationary  column  of  blood  included  in  an  artery  or  vein  between 
two  carefully  applied  aseptic  ligatures  within  tlie  living  body  may  remain 
fluid  for  weeks  (Glenard,  Baumgarten).  Slow  circulation,  however,  in 
combination  with  lesions  of  the  cardiac  or  vascular  wall,  or  witli  the  presence 
of  micro-organisms  or  other  chaaigcs  in  the  blood,  is  an  important  predis- 
posing cause  of  thrombosis,  and  frequently  determines  the  localisation  of 
the  thrombus.  This  is  evident  from  tlie  relative  infrequency  of  thrombi  upon 
diseased  patches  of  the  inner  coat  of  large  arteries  in  contrast  with  their 
frequency  upon  similar  patches  in  the  small  arteries  and  in  tlie  veins;  and 
in  general  from  the  predilection  of  thrombi  for  those  parts  of  the  circulatory 
channels  in  which  the  blood-flow  is  normally,  or  as  the  result  of  disease,  slow. 
Extensive  injur}'  to  the  walls  of  arteries  may  be  experimentally  produced 
without  resulting  tlirombosis. 

Eberth  and  Schimmelbusch  find  that  under  normal  conditions  the  platelets 
circulate  with  the  red  corpuscles  in  the  axial  blood-current,  but  make  their 
appearance  in  the  outer  still  zone  when  the  rapidity  of  the  circulation  is 
sufficiently  diminished,  iloderate  slowing  is  attended  by  tlie  accumulation 
of  white  corpuscles  in  this  zone,  while  a  furtJicr  slackening  of  tlie  stream  is 
characterised  by  fewer  leucocytes  and  more  platelets  in  the  peripheral  layer. 
Mere  slowing  of  the  circulation,  however,  docs  not  suffice  to  form  thrombi ; 
there  must  be  some  al)nonnulity  of  the  inner  lining  of  the  vessel-wall,  with 
which  the  platelets  are  brought  into  contact,  in  order  to  induce  the  viscous 
metamorphosis  of  these  bodies  essential  in  the  formation  of  plugs.    Hence 


THEOMBOSIS  123 

Eberth  and  Schimmelbusch  conclude  that  it  is  only  by  the  combination  of 
slowing  of  the  circulation  with  changes  in  the  inner  lining  that  the  formation 
of  white  thrombi  can  be  explained. 

Von  Eecklinghausen  attaches  more  importance  to  a  whirling  or  eddying 
motion  (Wirbelbewegung)  than  to  mere  slowness  of  tlie  circulation.  He 
has  pointed  out  that  eddies  are  produced  when  the  blood  enters  normally  or 
pathologically  dilated  channels  from  smaller  ones,  or  passes  into  a  cul-de-sac, 
or  over  obstructions;  and  he  has  considered  in  an  interesting  way  the  special 
conditions  causing  this  motion  and  its  influence  upon  the  production  of 
thrombi.  This  irregularity  of  the  blood-curr«nt  will  be  referred  to  again  in 
considering  the  localisation  of  venous  thrombi  (p.  138).  Von  Reckling- 
hausen's observations  make  a  valuable  contribution  to  our  knowledge  of  the 
mechanical  disturbances  of  the  circulation  which  favour  the  development 
of  thrombi. 

Thrombi  attributed  to  slowing  of  the  blood-current,  often  combined  with 
eddying  motion  of  the  blood,  are  called  stagnation-thrombi.  Of  these  two 
groups  are  distinguished:  (a)  those  due  to  local  circulatory  disturbances, 
as  from  interruption  or  narrowing  of  the  lumen  of  vessels  by  ligation  or 
compression,  or  from  circumscribed  dilatations,  as  aneurysms  or  varices ;  and 
(b)  marantic  thrombi  resulting  from  weakened  heart's  action,  with  conse- 
quent feebleness  of  the  general  circulation.  Virchow  gave  the  name  "  ma- 
rantic thrombi ''  to  all  or  nearly  all  thrombi  complicating  or  following 
anaemic  and  cachectic  states,  general  infective  diseases — as  enteric  fever, 
typhus  fever,  and  the  like,  and  certain  constitutional  diseases.  He  con- 
sidered a  condition  of  marasmus,  or  great  prostration,  to  be  tlie  common 
underlying  factor.  As  we  shall  see  subsequently,  there  are  serious  objections 
to  this  explanation  of  these  thromboses,  which  indeed  constitute  the  class  of 
chief  medical  interest.  The  designation  "  marantic  thromboses  "  for  this 
group  is  still,  however,  in  common  use.  Although  it  is  proper  in  these  groups 
of  thrombi  to  emphasise  the  mechanical  disturbances  of  the  circulation  as  an 
important  accessory  factor,  it  is  evident,  from  what  has  been  said,  that  the 
class  of  stagnation-thrombi  cannot  be  maintained  in  the  strict  sense  origin- 
ally advocated  by  Virchow.  Other  factors,  especially  lesions  of  the  walls  of 
the  heart  or  vessels,  enter  decisively  into  their  causation. 

Contact  of  the  Blood  with  Ahnormal  Surfaces.  Lesions  of  the  Cardiac  and 
Vascular  Walls. — It  is  universally  recognised  that  the  influence  of  the  endo- 
thelial lining  of  the  vascular  channels  in  maintaining  the  fluid  state  of  the 
blood  is  of  the  first  importance.  This  influence  appears  to  be  partly  physical 
and  partly  chemical.  The  smooth,  non-adhesive  character  of  the  inner  sur- 
face of  the  heart  and  vessels  is  the  physical  property  which  comes  primarily 
into  consideration.     Whereas  the  introduction  of  such  foreign  bodies  as 


124  THROMBOSIS 

threads,  or  bristles  with  rough  surface,  into  the  circulation  is  an  efficient 
cause  of  thrombosis,  perfectly  smooth,  indifferent  bodies,  as  small  glass  balls, 
may  be  introduced  without  causing  any  coagulation  (Zahn).  Freund  has 
shown  that  blood  collected  with  proper  precautions  in  vessels  lined  with  oil 
or  vaseline  remains  fluid  for  a  long  time.  Mere  contact  with  a  foreign 
surface,  therefore,  does  not  suffice  to  induce  clotting;  the  result  depends 
upon  the  character  of  this  surface.  Freund  concludes  that  the  essential 
thing  is  that  the  surface  shall  be  such  as  to  permit  adhesion  to  occur  between 
it  and  the  corpuscles,  particularly  the  red  corpuscles ;  the  normal  lining  of 
the  blood-vessels  being  characterised  by  the  absence  of  this  adhesive  property. 
Without  adopting  Freund's  theory  of  coagulation,  which  does  not  here 
concern  us,  we  can  apply,  with  much  satisfaction  in  the  explanation  of  many 
thrombi,  his  observations  concerning  the  importance  of  adhesive  surfaces  in 
causing  coagulation.  There  should  also  be  taken  into  consideration  the 
damage  known  to  be  inflicted  by  adhesive  contact  with  abnormal  surfaces 
upon  platelets  or  red  corpuscles;  if  these  be  regarded  as  the  source  of  the 
granular  material  and  platelets  in  thrombi. 

Changes,  therefore,  which  impair  or  destroy  the  smooth,  non-adhesive 
surface  of  the  normal  inner  lining  of  the  vessels  play  an  important  part  in 
the  etiology  of  tlirombosis ;  and  thrombi  thus  caused  may  be  called  adhesion- 
thrombi.  The  efficiency  of  these  lesions  in  causing  thrombi  is  increased  if, 
by  projection  into  the  lumen,  they  obstruct  the  blood-flow;  or  by  their  rough, 
irregular  surface  set  up  an  eddying  motion  of  the  blood. 

Although  we  have  very  little  definite  information  about  any  chemical 
activities  of  the  normal  vascular  endothelium  concerned  in  the  preservation 
of  the  fluidity  of  the  circulating  blood,  there  is  evidence  that  lesions  of  the 
intima,  through  chemical  as  well  as  physical  influences,  may  incite  throm- 
bosis. That  necrotic  endothelial  and  intimal  cells  may  liberate  fibrin- 
ferment  is  in  accordance  with  both  physiological  and  pathological  observa- 
tions relating  to  the  origin  of  this  ferment  from  dead  or  disintegrated  proto- 
plasm in  general.  Reference  has  already  been  made  to  observations  of  Zenker 
indicating  the  coagulative  influence  of  necrotic  endothelium,  and  of  the 
intima  deprived  of  endothelium. 

Strong  support  for  a  belief  in  the  participation  of  chemical  substances  in 
the  causation  of  certain  thrombi  due  to  intimal  lesions  is  to  be  foimd  in  con- 
trasting the  effects  of  mere  traumatism  with  those  of  traumatism  combined 
with  infection  of  the  intima.  This  has  been  especially  brought  out  in  the 
experimental  studies  of  valvular  lesions  of  the  heart.  Aseptic  laceration 
of  the  cardiac  valves  generally  leads  to  but  slight  production  of  thrombi 
upon  the  injured  surfaces;  whereas  the  same  traumatic  lesions,  combined 
with  the  lodgment  and  growth  of  pyogenetic  bacteria,  are  iLsually  attended 


THROMBOSIS  125 

by  the  formation  of  considerable  thrombotic  vegetations.  The  differences  in 
the  result  can  hardly  be  explained  by  differences  in  the  physical  characters  of 
the  lesions  in  the  tvvo  cases ;  but  we  have  no  definite  knowledge  concerning  tlie 
nature  and  mode  of  action  of  the  chemical  bacterial  products  concerned  in 
causing  the  thrombi.  We  may  draw  the  conclusion  that  lesions  of  the  intima, 
apart  from  their  more  manifest  characters,  may  possess  certain  specific 
properties  especially  favourable  to  the  production  of  thrombi. 

The  most  important  of  the  structural  changes  of  the  vascular  and  cardiac 
walls  which  cause  thrombosis  are  those  due  to  inflammation,  atheroma,  calci- 
fication, necrosis,  other  degenerations,  tumours,  compression,  and  injury. 
Here  again  may  be  emphasised  the  importance  of  retardation  and  other 
irregularities  of  the  circulation  in  rendering  these  various  lesions  effective 
causes  of  thrombosis.  The  aorta,  for  example,  may  be  the  seat  of  most 
extensive  deforming  endarteritis,  with  irregular  projecting  calcific  plates  and 
ragged  atheromatous  ulcers,  without  a  trace  of  thrombotic  deposit.  The 
forcible  pulsating  current  prevents  the  adhesion  and  accumulation  of  the 
formed  elements  consituting  the  beginning  thrombus,  or  quickly  washes 
them  away.  The  presence  in  some  instances  of  white  mural  thrombi  in  the 
aorta  upon  an  intima  apparently  but  slightly  damaged  indicates  the  impor- 
tance of  certain  specific,  although  little  imderstood,  characters  of  intimal 
lesions  in  association  with  changes  in  the  blood. 

Foreign  bodies,  which  have  penetrated  the  blood-channels  and  set  up 
thrombosis,  have  been  observed  repeatedly  in  human  beings,  especially  in 
the  heart  and  abdominal  veins.  Such  accidents  have  followed  swallowing 
fish-bones,  needles,  nails,  bits  of  wire  and  the  like.  A  blood-clot  or  thrombus 
in  a  vessel,  or  projecting  into  the  lumen  from  a  wound  of  the  vessel,  may 
itself  be  looked  upon  as  a  foreign  body,  and  lead  to  further  extension  of  the 
thrombus.  There  seems  to  be  a  certain  self-propagating  power  in  a  throm- 
bus. Similar  effects  are  produced  by  the  entrance  of  large  parasites,  such 
as  distomata,  by  the  invasion  of  tumour-masses,  and  by  the  penetration  of 
parench}Tnatous  cells  into  the  circulatory  channels  (p.  228). 

Infective  Thrombi.  Tliromho-Phlehitis. — Phlebitis,  as  a  cause  of  throm- 
bosis, has  reacquired  within  the  last  few  years  so  much  importance  that  it 
is  here  singled  out  from  other  lesions  of  the  vascular  wall  for  special 
consideration. 

In  the  first  half  of  the  present  century,  mainly  through  the  influence  of 
John  Hunter  and  of  Cruveilhier,  thrombosis  was  by  many  regarded  only 
as  an  expression  of  inflammation  of  the  inner  lining  of  the  vessels.  The 
material  composing  the  thrombus  was  considered  to  be,  at  least  in  part, 
an  exudate  of  coagulable  lymph  from  the  inflamed  vascular  wall.  Virchow, 
by  his  monumental  work  on  thrombosis  and  embolism,  dating  from  1846, 


126  THROMBOSIS 

reversed  this  order  of  things,  and  made,  for  the  great  majority  of  cases, 
the  thrombus  the  primary  and  essential  phenomenon,  and  the  inflammation 
of  the  wall,  if  present,  a  merely  secondary  effect.  Phlebitis  disappeared, 
as  a  chapter,  from  works  on  internal  medicine,  and  thrombosis  took  its  place. 
Witliin  recent  years,  and  again  chiefly  through  the  work  of  French  investi- 
gators, the  pendulum  has  swung  back,  and  phlebitis  has  once  more  come  to 
the  front  as  a  common  and  important  cause  of  thrombosis,  and  resumed  an 
important  place  in  many  systematic  treatises  on  medicine.  This  rehabili- 
tation of  phlebitis  is  due  mainly  to  bacteriological  investigations  of  throm- 
bosed vessels,  especially  of  the  so-called  marantic  thrombi  of  infective  and 
cachectic  diseases. 

The  distinction  between  bland  thrombi  and  infective  thrombi  is  an  old 
and  important  one.  The  thrombi  in  septic  and  su])purative  phlebitis,  con- 
cerned especially  in  pya?mic  processes  and  surgical  affections  were  for  a 
long  time  the  chief,  indeed  almost  the  only  recognised  representatives  of 
the  class  of  infective  thrombi.  There  has  been  a  gradual  extension  of  the 
domain  of  infective  thrombosis,  until  now  many  thrombi,  previously  classi- 
fied as  bland,  are  considered  to  be  of  infective  origin.  This  is  notably  true 
of  a  large  number  of  thrombi,  fonnerly  and  still  often  called  marantic,  com- 
plicating many  infective  diseases,  wasting  and  cachectic  conditions,  and 
anaemia.  In  1887  Weigert  stated  that  by  means  of  his  fibrin-stain  he  had 
found  unsuspected  micro-organisms  in  marantic  thrombi  with  surprising 
frequency ;  and  since  then  there  have  been  numerous  similar  observations,  as 
well  as  not  a  few  negative  ones.  In  France  the  studies  of  Comil  and  his 
pupils,  especially  Widal,  and  of  Vaquez  have  had  the  greatest  influence  in 
developing  the  doctrine  of  the  mycotic  origin  of  this  class  of  thrombi,  and 
particularly  that  of  primary  phlebitis  as  the  cause  of  these  thromboses.  It 
should  not  be  forgotten  that  Paget,  in  18GG,  contended  for  the  primarily 
phlebitic  nature  of  thrombosis  in  gout. 

Plilegmasia  alba  dolens  of  the  puerperium  is  the  prototype  of  this  class 
of  thromboses.  In  the  articles  on  various  infective  diseases,  particularly 
enteric  fever  (see  Allbutt*s  "  System  of  Medicine,"  I,  p.  817)  and  influenza 
(AUbutt's  "  System  of  Medicine,"  I,  p.  683),  attention  has  l>een  called  to  the 
occurrence  of  thrombosis  as  a  complication  or  sequel.  Similar  thromboses 
occur  in  pneumonia,  typhus,  acute  rlieumatism,  erysipelas,  cholera,  scarlatina, 
variola,  tuberculosis,  syphilis — in  fact  with  greater  or  less  frequency  in 
nearly  all  acute  and  chronic  infections.  Likewise  in  chlorosis,  gout,  leu- 
kaemia, senile  del)ility,  and  chronic  wasting  and  cachectic  diseases,  particu- 
larly cancer,  thrombosis  is  a  recognised  complication.  The  more  important 
associations  of  thrombosis  with  these  various  diseases  will  be  considered  more 
in  detail  subsequently  (p.  119). 


THROMBOSIS  127 

These  various  thromboses,  occurring  very  rarely  as  primary  affections, 
usually  secondary  to  infective  or  constitutional  diseases,  compose  the  great 
majority  of  those  of  medical,  as  distinguished  from  surgical  interest.  Clini- 
cally and  anatomically  they  undoubtedly  have  much  in  common.  Is  there 
any  common  etiological  point  of  view  from  which  they  may  be  regarded? 
Virchow  thought  so  in  calling  them  marantic  thrombi,  and  attributing  their 
causation  to  enfeebled  circulation.  The  same  causative  factor  still  remains 
the  underlying  one  with  those  who,  like  Cohnheim,  interpolate  nutritive 
changes  in  the  endothelium  between  the  slow  circulation  and  the  beginning 
of  the  thrombus. 

Impaired  circulation  cannot  serve  as  a  common  etiological  shelter  for 
this  whole  class  of  thromboses.  There  is  no  definite  and  constant  relationship 
between  the  condition  of  the  circulation  and  the  occurrence  of  these  thrombi. 
While  many  appear  during  great  debility,  others  of  the  same  nature,  and 
often  in  the  same  disease,  occur  when  the  heart's  action  is  not  notably  weak. 
Thrombosis  may  ensue  early  in  influenza.  It  is  oftener  a  sequel  than  an 
accompaniment  of  enteric  fever.  On  the  other  hand,  the  circulation  may 
be  extremely  feeble  for  days  without  the  appearance  of  thrombosis. 

Many  of  these  so-called  marantic  thrombi  are  unquestionably  of  infective 
origin.  Vaquez,  in  his  monograph  on  phlebitis  of  the  extremities,  published 
in  1894,  has  brought  together  the  results  of  the  observations  of  others,  and 
especially  those  of  his  own  and  Widal's  investigations,  which  demonstrate 
that  l)acteria  are  often  present  in  these  thrombi  and  in  the  adjacent  vascu- 
lar wall.  Since  the  appearance  of  Vaquez'  monograph  there  have  been  a 
number  of  confirmatory  observations.  Widal  emphasises  the  importance  of 
searching  for  bacteria  in  fresh  thrombi,  and  in  the  autochthonous  part  of 
the  thrombus  and  the  adjacent  wall  of  the  vessel.  The  largest  contingent 
of  positive  results  has  been  fvirnished  by  the  examination  of  puerperal 
thrombi — many  of  which  indeed  are  examples  of  septic  thrombo-phlebitis, 
and  of  the  marantic  thrombi  of  chronic  pulmonary  tuberculosis  ;  but  bacteria 
have  also  been  found  in  thrombi  complicating  or  following  typhoid  fever, 
influenza,  pneumonia,  cancer,  and  other  infective  and  cachectic  conditions. 

In  relatively  few  instances  has  the  specific  micro-organism  of  the  primary 
disease,  as  the  typhoid  or  the  tubercle  bacillus,  for  example,  been  present  in 
the  thrombus;  more  frequently  secondary  invaders,  especially  streptococci 
and  other  pyogenetic  bacteria,  have  been  detected :  so  that  the  thrombosis  is 
considered  to  be  oftener  the  result  of  some  secondary  infection  than  of  the 
primary  one.  Colon  bacilli  have  been  found  in  typhoidal  and  other  thrombi ; 
but  as  these  bacteria  are  found  so  commonly  in  the  blood  and  organs  after 
death  from  all  sorts  of  causes,  no  great  importance  can  be  attached  to  their 
mere  demonstration  without  some  further  evidence  of  their  pathogenetic 


128  THROMBOSIS 

activity.  As  might  be  expected,  streptococci  are  the  bacteria  found  most 
frequently  in  puerperal  thromboses.  Singer  believes  that  gonorrhoea!  infec- 
tion is  also  a  possible  factor. 

Not  only  in  thrombi  of  infective  diseases  but  also  in  cachectic  thromboses 
have  bacteria,  and  here  again  most  frequently  pyogenetic  forms,  been  demon- 
strated. Xor  is  this  surprising  when  we  consider  the  frequency  of  secondar}' 
infections  in  chronic  diseases,  especially  as  a  terminal  event;  as  has  been 
clearly  brought  out  in  the  analyses,  by  Flexner,  of  the  autopsies  at  the  Johns 
Hopkins  Hospital,  where  bacteriological  examination  is  a  routine  procedure 
at  the  post-mortem  table.  Many  of  these  infections  are  unsuspected  during 
life. 

The  supposition  that  in  all  of  these  eases  the  bacteria  are  accidentally  or 
secondarily  present,  and  in  no  way  concerned  in  the  causation  of  the  thrombi, 
is  extremely  improbable.  They  are  often  in  such  number,  in  such  arrange- 
ment and  associated  with  such  lesions,  that  they  must  have  multiplied  in  the 
thrombus  and  in  the  vessel  wall. 

The  problem  whether  the  bacteria  have  led  to  thrombosis  by  first  invading 
the  vascular  wall  and  setting  up  inflammation  is  not  solved  by  the  mere 
demonstration  of  their  presence.  Certainly,  in  some  instances,  this  sequence 
of  events  is  plainly  indicated  by  the  microscopical  appearances ;  but  in  many 
it  is  impossible  to  decide  to  what  extent  inflammatory  changes  in  the  wall 
antedated  the  thrombus,  for  the  latter,  especially  when  infected  by  bacteria, 
induces  a  secondar}-  angeiitis.  Opportunities  to  study  very  recent  infective 
marantic  thrombi  with  reference  to  this  point  are  not  common. 

In  a  case,  which  I  examined,  of  multiple  venous  thrombosis  complicating 
leucocythfpmia,  there  was  a  primary  mycotic  endophlebitis  with  secondary 
thrombosis.  There  was  a  secondary  streptococcus  infection.  In  the  intima 
of  the  thrombosed  vessels  were  numerous  scattered  foci  in  which  large  num- 
bers of  streptococci  were  present.  In  these  areas  there  was  necrosis  of 
endothelial  and  other  intimal  cells,  with  proliferation  of  surrounding  cells 
and  many  polynuclear  leucocytes.  These  foci  formed  little  whitish  eleva- 
tions capped  with  platelets,  fibrin,  and  leucocytes ;  the  whole  presenting  an 
appearance  similar  to  that  of  endocardial  vegetations.  There  was  marked 
nuclear  fragmentation  both  in  the  infected  intima  and  in  the  thrombus. 
Fresh  mixed  thrombi,  containing  fewer  streptococci,  were  connected  ^vith 
these  phlebitic  vegetations.  Although  the  vasa  vasorum  were  hyperaemic, 
and  were  the  seat  of  a  moderate  migration  of  leucocytes,  streptococci  were 
absent  from  the  adventitia;  and  the  appearances  spoke  decidly  for  the  direct 
penetration  of  the  streptococci  from  the  circulating  blood  into  the  intima.  I 
have  examined  three  other  similar  cases.  A  similar  form  of  mycotic  endo- 
phlebitis has  been  described  by  Vaquez  (endophl^bite  vegetante).    In  other 


THROMBOSIS  129 

cases  the  intima  is  more  diffusely  inflamed.  After  a  short  time  there  is  no 
distinct  line  of  demarcation  between  the  thrombus  and  the  intima,  and  all 
of  the  coats  of  the  vessel  are  more  or  less  inflamed. 

Although  the  bacteria  found  in  the  intima  may  gain  access  from  without 
through  the  vasa  vasorum,  or  the  lymphatics,  it  is  probable  that  in  the  class 
of  cases  here  under  consideration  they  more  frequently  enter  directly  from 
the  blood  circulating  in  the  main  channel.  There  may  be  very  extensive 
bacterial  inflammation  of  the  venous  wall,  even  with  bulging  of  the  intima 
into  the  lumen,  without  any  thrombosis. 

We  do  not  possess  sufficiently  numerous  and  careful  bacteriological  exami- 
nations of  the  thrombi  of  infective  and  wasting  diseases  to  enable  us  to  say 
in  what  proportion  of  cases  they  contain  micro-organisms.  It  is  certain 
that  in  many  instances  such  examinations  have  yielded  negative  results.  It 
is  quite  possible  that  in  some  of  these  negative  cases  bacteria,  originally 
present,  have  died  out;  but  although  by  some  authors  much  use  is  made 
of  this  explanation,  it  is  not  in  general  a  satisfactory  one.  ]\Iany  of  the 
examinations  were  of  thrombi  sufficiently  recent  to  exclude  this  possibility. 
To  explain  these  non-bacterial  cases,  the  French  writers  assume  the  exis- 
tence of  a  primary  toxic  endophlebitis,  the  toxins  being  either  of  bacterial 
origin  or  derived  from  other  sources.  Ponfick,  many  years  ago,  called  atten- 
tion to  the  occurrence  of  degenerations  of  the  vascular  endothelium  in 
infective  diseases ;  and  there  can  be  no  doubt  of  the  frequency  of  both  degen- 
erative and  inflammatory  changes  of  the  intima  in  toxic  and  infective 
conditions. 

A  lesion  which  I  have  seen  in  the  intima  of  veins  (less  frequently  of 
arteries)  in  typhoid  fever,  diphtheria,  variola,  and  other  infective  diseases, 
is  a  nodular,  sometimes  a  more  diffuse,  accumulation  of  lymphoid  and 
endothelioid  cells  beneath  the  endothelium.  These  cells,  as  weU  as  the 
covering  endothelium,  may  undergo  necrosis ;  indeed  the  appearances  some- 
times suggest  primary  necrosis  with  secondary  accumulation  of  wandering 
cells  and  proHferation  of  fixed  cells.  These  foci  are  not  unlike  the  so-called 
lymphomatous  nodules  found  in  the  liver  in  typhoid  and  other  infections. 
They  may  unquestionably  be  the  starting-point  of  thrombi,  as  has  been 
shown  by  Mallory  in  his  study  of  the  vascular  lesions  in  typhoid  fever. 
Although  this  form  of  endophlebitis  or  endarteritis  resembles  that  demon- 
strably caused  by  the  actual  presence  of  bacteria  in  the  intima,  bacteria  are 
often  absent,  even  in  the  fresh  lesions;  so  that  it  is  reasonable  to  suppose 
that  the  affection  may  be  caused  by  toxins.  I  think  that  this  toxic  endan- 
geiitis  is  of  importance  in  the  causation  of  thrombosis  complicating  infective 
and  cachectic  states. 


130  THROMBOSIS 

There  are,  however,  instances  of  so-called  marantic  thrombosis  where  no 
visible  alteration  of  the  intima  can  bo  made  out  at  the  site  of  the  thrombus, 
or  only  the  slight  fatty  degeneration  of  the  endothelium  which  is  such  an 
extremely  common  condition  that  it  does  not  afford  a  satisfactory  explanation. 

It  is  obvious  that  bacteria  are  likely  to  find  especially  favourable  oppor- 
tunities to  gain  lodgment,  and  toxic  substances  to  do  injury,  in  situations 
where  the  blood-current  is  slow  and  thrown  into  eddies ;  but  the  localisation 
in  these  situations  of  thromboses  complicating  infective  and  chronic  diseases 
has  perhaps  been  unduly  emphasised.  These  thromboses  may  occur  else- 
where, even  in  the  aorta  and  larger  arteries.  Pre-existing  diseases  of  the 
veins,  especially  chronic  endophlebitis  and  varicosities,  are  conditions  predis- 
posing to  infective  and  cachectic  thromboses. 

While  we  are  justified  in  assigning  a  far  more  prominent  place  to  the 
agency  of  micro-organisms  and  to  primary  phlebitis  in  the  etiology  of 
thrombosis  than,  until  recent  years,  has  been  customary  since  Virchow's  fun- 
damental investigations,  recent  attempts  to  refer  all  thromboses,  formerly 
called  marantic,  to  the  direct  invasions  of  microorganisms  and  to  phlebitis 
go  beyond  demonstrated  facts.  We  have  not  at  present  any  satisfactory 
bacteriological  and  anatomical  substratum  for  so  wide  a  generalisation. 
The  whole  field,  although  difficult,  is  an  inviting  and  fruitful  one  for  fur- 
ther investigation.  The  clinical  arguments  in  favour  of  the  phlebitic  origin 
of  thromlx)sis  will  be  considered  below  (p.  172). 

What  has  been  said  regarding  the  relation  of  phlebitis  to  thrombosis 
complicating  infective  and  constitutional  diseases  applies  also  to  that  of 
arteritis  to  the  similar  arterial  thromboses  which,  although  less  common 
than  the  venous,  are  more  frequent  than  was  formerly  supposed ;  this  will  ap- 
pear when  we  take  up  the  association  of  thrombosis  with,  particular  diseases 
(p.  149). 

It  is  of  course  understood  that  the  preceding  remarks  on  the  relation  of 
phlebitis  and  arteritis  to  thrombosis  relate  only  to  the  medical  thromboses, 
and  not  to  the  septic  and  suppurative  thrombophlebitides  of  the  surgeon, 
of  the  bacterial  origin  of  which  there  is  no  question ;  although  these  latter 
may  l)e  concerned  in  diseases,  such  as  suppurative  pylephlebitis,  which  are 
in  the  province  of  the  physician. 

Chemical  Changes  in  the  Blood.  Ferment-Thromhi. — The  old  ideas  of 
chemical  changes  in  the  blood  as  causes  of  intravascular  clotting,  embodied 
in  such  terms  as  acre  coagulatorium,  hyperinosis,  inopexia,  are  now  of  his- 
torical interest  only.  There  appears  to  be  no  definite  and  constant  relation 
between  the  amount  of  fibrin  obtainable  from  the  blood,  or  the  rapidity  of 
its  coagulation  in  the  test  tube,  and  the  occurrence  of  thrombosis  in  human 
beings.     Peripheral  thrombosis  is  a  less  common  complication  of  pneu- 


THROMBOSIS  131 

monia  and  acute  articular  rheumatism,  which  are  characterised  by  high 
fibrin-content  of  the  blood,  than  of  enteric  fever  and  certain  cachectic 
states  in  which  the  fibrin-content  is  approximately  normal  or  reduced. 

In  dogs  whose  blood  was  rendered  incoagulable  by  injection  of  "  pep- 
tone "  (albumose)  Schimmelbusch  produced  platelet-thrombi  experimen- 
tally. On  the  other  hand,  Sahli  with  Eguet  observed  no  collection  of 
platelets  or  formation  of  thrombi  around  hog's  bristles  or  silk  threads 
inserted  into  the  jugular  veins  of  rabbits  having  incoagulable  blood  from 
injection  of  leech  extract;  although  control  experiments  regularly  gave 
positive  results.  These  latter  experiments  show  that  chemical  changes  in 
the  blood  may  influence  the  process  of  thrombosis. 

The  main  support  of  the  belief  entertained  by  some  that  the  liberation  of 
fibrin-ferment  in  the  general  blood-stream  is  an  important  cause  of  human 
thrombosis,  is  based  on  the  results  of  experiments  which  demonstrate  that 
the  injection  of  various  substances  into  the  circulation  may  cause  intravas- 
cular clottings.  The  most  important  of  the  substances  which  have  been 
observed  to  produce  this  effect  are  laky  blood  (Naunyn),  biKary  salts 
(Ranke),  ether  (jSTaunyn,  Hanau),  fresh  defibrinated  blood  (Kohler), 
emulsions  or  extracts  from  cells,  especially  lymphoid  cells  (Groth,  Woold- 
ridge),  transfusion  of  blood  (Landois,  Ponfick),  and  snake-venom  (C.  J. 
Martin,  art.  "Snake-poison  and  Snake-bite,"  vol.  iii.  p.  819).  The  coagu- 
lating effect  of  laky  blood  is  attributable  to  the  stromata  of  red  corpuscles 
rather  than  to  dissolved  haemoglobin  (Wooldridge).  The  coagulating  prin- 
ciple here,  as  well  as  of  the  various  tissue-extracts,  is  believed  to  be  a  nucleo- 
proteid  which,  by  combination  with  calcium,  forms  the  fibrin-ferment.  It 
is  to  the  presence  of  this  ferment  or  the  subsequent  liberation  of  the  ferment 
that  the  dangerous  intravascular  clots  following  the  injection  of  defibrinated 
blood  or  the  transfusion  of  foreign  blood  are  due.  The  coagulative  effect  of 
snake-venom  under  certain  conditions  is  referred  by  Halliburton  to  pro- 
teoses free  from  phosphorus,  and  therefore  not  nucleo-proteids.  The  action 
of  snake-venom  upon  coagulation  is  probably  analogous  to  that  of  various 
toxic  albumoses,  bacterial  and  vegetable.  They  are  in  general  to  be  ranked 
among  anti-coagulating  substances;  but  the  result  varies  with  the  dose, 
the  manner  of  injection,  and  other  circumstances.  Wooldridge  has  shown 
that  thromboses  are  particularly  prone  to  occur  in  the  territor}^  of  the  portal 
system  after  the  injection  of  various  substances  favouring  coagulation. 
Fibrin-ferment  may  be  used  up  in  the  process  of  intravascular  clotting,  so 
that  after  this  has  taken  place  the  remaining  blood  may  be  incoagulable. 

Interesting  as  these  experimental  results  are  to  the  physiologist,  and 
with  reference  to  the  theories  of  the  coagulation  of  blood,  it  is  difficult  to 
utilise  them  in  any  satisfactory  way  in  the  explanation  of  ordinary  human 


132  THROMBOSIS 

thrombosis.  Most  of  the  experimenters  make  no  statement  as  to  the  micro- 
scopical structure  of  the  intravascular  clots,  which  are  described  generally 
as  soft,  dark  red  masses;  and  they  seem  to  identify  them  with  ordinary 
human  thrombi,  being  apparently  not  familiar  with  the  researches  on  the 
peculiar  constitution  of  the  latti^r.  Some  of  the  substances  used  for  the 
experiments  cause  precipitates  in  the  blood,  and  many  are  very  destructive 
to  the  red  corpuscles.  Hanau,  however,  has  shown  that  masses  of  platelets 
may  be  present  in  these  clots. 

Conditions  analogous  to  those  set  up  in  these  experiments  may  occur  in 
human  beings ;  but  they  are,  so  far  as  we  know,  most  exceptional.  Especially 
do  we  lack  satisfactory  observations,  in  cases  of  thrombosis  in  human  beings, 
of  increase  of  fibrin-ferment  in  the  blood.  Considerable  quantities  of 
fibrin-ferment,  more  than  are  likely  to  be  liberated  under  any  probable  cir- 
cumstances in  man,  can  be  injected  into  the  circulation  without  causing 
coagulation.  Still  it  is  possible  that  the  mechanism  by  which  this  excess  of 
fibrin-ferment  is  neutralised  and  coagulation  prevented  may  be  paralysed 
under  certain  conditions.  There  are  certain  instances  of  rapidly-formed 
red  thrombi  in  vessels  with  apparently  normal  walls  which,  in  the  absence 
of  other  explanation,  it  would  be  very  convenient  to  refer  to  ferment-intoxi- 
cation. Kohler  and  Hanau  consider  that  many  thrombi,  especially  those 
complicating  infective  and  cachectic  states,  are  best  explained  by  supposing 
a  liberation  of  fibrin-ferment  in  the  blood,  and  they  call  them,  therefore, 
ferment- thrombi. 

Hayem  designates  as  thrombi  from  precipitation  (thromboses  par  pre- 
cipitation) many  which  others  call  ferment-tlirombi ;  especially  those  fol- 
lowing injection  of  various  destructive  substances  into  the  circulation,  and 
those  caused  by  burns  and  freezing. 

Silbermann  and  others  assert  tlmt  thrombosis,  particularly  multiple 
capillary  thrombosis,  plays  an  important  part  in  extensive  superficial  burns, 
and  in  poisoning  with  various  substances  destructive  to  the  blood  corpuscles, 
such  as  anilin,  potassium  chlorate,  arsenic,  phosphorus,  sublimate,  carbon- 
0U8  oxide,  illuminating  gas.  These  views  need  further  confirmation  befonj 
they  can  be  accepted,  as  several  obser\'ers  have  obtained  only  negative  results 
in  searching  for  thrombi  in  the  same  class  of  cases. 

Notwithstanding  the  lack  of  a  substantial  basis  of  demonstrated  facts  for 
the  opinion  that  human  thrombosis  is  often  caused  by  liberation  of  fibrin- 
ferment  in  the  general  blood-stream,  it  would  be  quite  unreasonable  to  sup- 
pose that  chemical  changes  of  the  blood  are  without  influence  upon  the 
occurrence  of  thrombosis  in  man.  Indeed,  in  infective  and  t«xic  conditions 
such  chajiges  are  doubtless  tlie  underlying  factors.  Both  tlie  circulatory 
disturbances  and  the  alterations  in  the  vascular  wall  to  which  we  attribute 


THROMBOSIS  133 

the  production  of  thrombi  are  tlie  result  of  damage  done  to  the  heart  and 
vessels  by  bacterial  and  other  toxins.  More  than  this,  there  is  good  reason 
to  believe  that  alterations  in  the  formed  elements  of  tlie  blood,  caused  directly 
or  indirectly  by  toxic  substances,  are  of  great  significance  in  the  etiology  of 
thrombosis.  The  platelets  are  in  all  probability  cell-derivatives;  and  we 
may  well  suppose  tliat  damage  inflicted  upon  leucocytes  and  red  corpuscles 
may  favour  their  production,  and  that,  in  consequence  of  abnormal  com- 
position of  the  plasma,  the  platelets  themselves  may  more  readily  undergo 
viscous  metamorphosis,  and  form  plugs.  In  view  of  recent  observations  in 
favour  of  the  origin  of  platelets  from  red  corpuscles,  the  studies  of  Ehrlich, 
Maragliano,  von  Limbeck,  and  otliers,  concerning  degenerations  and  in- 
creased vulnerability  of  these  corpuscles  in  various  diseases,  are  of  interest 
with  reference  to  thrombosis;  but  it  must  be  confessed  that  we  cannot  at 
present  make  more  than  a  hypothetical  application  of  these  results  to  the 
explanation  of  certain  forms  of  thrombosis.  To  discuss  here  further  the 
hypotheses  upon  this  subject  would  be  barren  of  any  useful  result. 

Increase  of  Blood-Platelets. — In  view  of  the  essential  part  taken  by  blood- 
platelets  in  the  formation  of  thrombi,  it  is  important  to  inquire  whether 
thrombosis  can  be  brought  into  any  relation  with  a  pathological  increase  of 
these  elements.  Some  observations  of  the  existence  of  such  a  relationship 
are  liighly  suggestive. 

Especial  difficulties  are  encountered  in  the  efforts  to  enumerate  the  plate- 
lets on  account  of  their  small  size  and  their  viscid  consistence,  which  causes 
them  to  clump  together.  Brodie  and  Eussell  give,  as  the  norm,  one  platelet 
to  8.5  red  corpuscles;  or  about  635,000  per  cubic  millimetre.  This  estimate 
is  considerably  higher  than  that  obtained  by  others,  probably,  however,  by 
less  accurate  methods.  Van  Emden  gives  as  the  average  for  human  beings 
in  health  245,000 ;  which  corresponds  fairly  well  with  the  figures  of  Hayem, 
Cadet,  Afanassiew,  Muir,  Fusari,  and  Determann,  but  is  lower  than  those 
of  Laker  and  Prus. 

There  is  considerable  divergence  of  statement  as  to  the  number  of  platelets 
in  different  diseases.  This  number  is  markedly  increased  in  chlorosis 
(Muir),  of  which  thrombosis  is  a  well-recognized  complication.  The  plate- 
lets are  increased  in  post-hsemorrhagic  anaemia  (Hayem),  which  is  one  of 
the  remoter  causes  of  thrombosis.  There  is  evidence  that  haemorrhage  after 
childbirth,  and  in  the  course  of  various  diseases,  favours  the  occurrence  of 
thrombosis.  Several  observers  have  found  the  platelets  reduced  in  nimiber 
in  pernicious  anaemia,  which,  unlike  chlorosis,  is  rarely,  if  ever,  complicated 
by  thrombosis  (Hayem,  Birch-Hirsehfeld,  Beugnies-Corbeau).  In  purpura 
hgemorrhagica  there  is  extreme  diminution  of  platelets,  sometimes  amounting 
to  total  absence  (Denys,  Hayem,  Ehrlich,  van  Emden),  which  constitutes 


134  THROMBOSIS 

the  only  demonstrated  morpholo^eal  change  of  the  blood  in  this  disease. 
In  febrile  infections  there  is  often  a  correspondence  between  leucocytosis  and 
the  number  of  platelets.  Thus  in  influenza,  pneumonia,  erysipelas,  menin- 
gitis, and  septic  infections  the  number  of  platelets  is  often  increased,  in 
severe  cases  sometimes  diminished;  whereas  in  enteric  fever  and  malaria  it 
is  diminished  (Hayem,  Eeyne,  Tiirk,  Muir,  van  Emden).  The  disappear- 
ance of  leucocytosis  is  sometimes  followed  by  increase  of  platelets.  In  view 
of  the  greater  frequency  of  thrombosis  as  a  sequel  than  in  the  course  of  many 
acute  diseases,  the  recognition  by  Hayem  of  a  platelet  crisis  (crise  hemato- 
blastique)  is  interesting.  After  the  crisis  or  subsidence  of  certain  infective 
diseases  Hayem  observed  a  rapid  and  marked  increase  in  the  platelets.  This 
was  noted  after  pneumonia  and  enteric  fever.  Platelets  are  said  to  be  often 
increaesd  toward  the  end  of  pregnancy  aJid  after  delivery  (Ilayem,  Cadet). 
In  various  cachectic  conditions,  in  tuberculosis,  and,  in  general,  in  states  of 
bad  nutrition,  increase  is  the  rule.  Dr.  Muir  finds  that  in  spleno-medullary 
leucocytha^mia  the  platelets  are  notably  increased,  but  not  in  the  lymphatic 
form  (art.  "  Leucocytha^mia,"  AUbutt's  "  System  of  Medicine,"  V,  p.  6-iO). 
In  chronic  passive  congestion,  due  to  heari:  disease,  the  platelets  are  said  to 
be  diminislied  (van  Emden).  An  increase  of  platelets  in  various  conditions 
in  which  they  are  usually  diminished  can  often  be  attributed  to  complications. 
Upon  the  whole  there  is  much  in  suppori;  of  the  view  tliat  increase  of  platelets 
is  an  index  of  lowered  resistence  of  the  red  corpuscles. 

It  is  fair  to  say  tliat  some  of  the  foregoing  statements  regarding  the  con- 
dition of  the  platelets  in  various  diseases  need  further  confirmation,  and 
that  in  general  tlie  subject  is  difficult  and  has  been  insufficiently  investigated. 
Nevertheless  we  cannot  fail  to  have  our  attention  arrested  by  a  parallelism, 
in  many  instances,  between  disposition  to  thrombosis  and  increased  number 
of  platelets ;  although  in  others  no  such  relationship  is  apparent.  It  must 
suihce  to  call  attention  to  this  parallelism,  for  we  are  ignorant  of  the  under- 
lying factors. 

It  hardly  need  be  said  that  the  mere  increase  of  platelets  is  insufficient  to 
explain  the  occurrence  of  tlirombosis.  We  are  brought  back  here,  as  else- 
where, to  disturbance  of  the  circulation  and  changes  in  the  vascular  walls 
as  the  detenninants  of  the  localisation  of  thrombi;  while  we  must  recognise 
changes  in  the  chemistry^  and  morphology  of  tlie  blood  as  important  pre- 
disposing causes. 

IjOCALiSATiON.-:-Thrombosis  may  occur  in  any  part  of  the  circulatory 
system.  We  distinguish  therefore  arterial,  venous,  capillary,  and  cardiax3 
thrombi.  Lymphatic  vessels  may  likewise  become  plugged  with  fibrin, 
leucocytes,  or  foreign  material ;  such  as  tubercle,  cancer,  or  red  corpuscles. 

Arterial  Thromhi. — The  majority  of  arterial  thromboses  are  caused  by 
Borae  local  injury  or  disease  of  the  arterial  wall,  or  by  the  lodgment  of  an 


THROMBOSIS  135 

embolus.  Especially  important  are  the  arterio-sclerotic  thromboses  of  the 
brain,  heart,  and  extremities. 

Here  may  be  mentioned  the  varying  relations  of  arterial  thrombosis  to 
gangrene  of  the  extremities.  Thrombosis  of  arteries,  as  well  as  of  veins, 
may  be  secondary  to  varieties  of  gangrene  which  are  not  caused  by  primary 
plugging  of  the  arteries.  Senile  gangrene  is  caused  eitlier  by  embolism, 
which  may  lead  to  tlirombosis,  or  by  arterio-sclerosis,  usually  associated 
with  thrombosis.  In  various  infective  and  chronic  wasting  diseases  gan- 
grene may  result  from  primary  arterial  thrombosis  of  the  class  often  called 
marantic.  Many  of  these  thromboses  are  infective  in  origin;  but  we  have 
not  sufficient  information  to  warrant  the  assertion  that  all  are  caused  by 
micro-organisms. 

Of  especial  interest  is  tlie  relation  of  thrombosis  to  certain  forms  of 
so-called  "  spontaneous  "  gangrene  which  may  occur  in  middle  life,  or  even 
in  the  young,  and  are  often  preceded  by  definite  symptoms  indicative  of 
gradual  occlusion  of  the  arteries.  Von  Winiwarter  concluded  from  his  ex- 
aminations of  several  cases  that  the  primary  disease  is  an  obliterating  en- 
darteritis resulting  in  complete  closure  of  tlie  affected  vessels.  Zoege  von 
Manteuifel,  however,  finds  that  thrombosis  participates,  in  an  interesting 
way,  in  the  gradual  occlusion  of  the  arteries.  According  to  him,  by  the 
deposition  and  organisation  of  successive  layers  of  parietal  thrombi,  the 
arteries,  which  are  usually  the  seat  of  a  primary  sclerosis,  gradually  become 
filled  with  vascularised  connective  tissue.  Haga  considers  this  endarteritis 
thrombotica  to  be  syphilitic.  Hoegerstedt  and  Nemser  beheve  that,  in 
general,  the  deposition  and  organisation  of  parietal  thrombi  are  common  and 
important  processes  in  angio-sclerosis.  Von  Recklinghausen  has  described 
hyaline  thrombosis  of  small  arteries  in  spontaneous  and  arterio-spastic 
gangrene. 

The  action  of  infective  agents  in  the  causation  of  focal  and  diffuse  diseases 
of  tlie  arteries  is  receiving  constantly  increasing  attention.  The  occurrence 
of  acute  and  chronic  arteritis  as  a  result  of  various  infective  diseases — as 
enteric  fever,  typhus  fever,  acute  articular  rheumatism,  variola,  scarlatina, 
pneumonia,  endocarditis,  septicemia,  syphilis,  tuberculosis,  leprosy — is  now 
so  well  estahlished  that  it  is  reasonable  to  believe  that  the  arterial  throm- 
boses complicating  or  following  these  diseases  are  often  referable  to  an 
infective  arteritis. 

It  cannot  be  doubted  that  not  a  few  cases  reported  in  literature  as  primary 
arterial  thrombosis  are  to  be  attributed  to  embolism  wliich  was  overlooked. 
The  possible  sources  of  emboli  for  the  aortic  system  can  be  usually  controlled 
much  more  readily  than  those  for  the  pubnonary  arteries;  for  the  latter 
sources  embrace  all  the  svstemic  veins.     These  veins  may  contain  mural 


136  THEOMBOSIS 

thrombi,  or  in  places  occluding  thrombi,  which  give  no  signs  of  their  pres- 
ence. The  possibility  that  an  entire  thrombus  may  be  detached  and  trans- 
ported by  the  blood-current,  so  that  its  original  location  cannot  be  deter- 
mined, is  also  to  be  considered.  But,  after  all  has  been  said,  it  is  carrying 
scepticism  to  an  unjustifiable  extreme  to  refuse  to  admit  the  occurrence  of 
primar}'  arterial  thrombosis  in  infective,  cachectic,  and  anaemic  states,  under 
circumstances  where  the  localisation  cannot  be  attributed  to  arterio-sclerosis 
or  other  pre-existing  arterial  disease.  Mr.  Jonathan  Hutchinson  has  recently 
reported  observations  of  rapid  thrombosis  of  arteries  without  obvious  disease 
of  the  walls. 

The  most  frequent  site  of  arterial  thrombosis  is  in  the  extremities,  and 
far  more  frequently  in  the  lower  than  the  upper.  Arterial  thrombosis,  unlike 
venous,  occurs  on  the  right  side  as  often  as  on  the  left.  Other  situations, 
more  or  less  common,  are  the  cerebral,  pulmonary,  coronary  of  tlie  heart, 
mesenteric  arteries,  and  the  aorta  and  its  primary  branches. 

Venous  Thrombi. — These  may  result  from  local  causes,  such  as  traimia- 
tism,  compression,  phlebitis,  phlebo-sclerosis,  varix  (266),  inflammation 
or  other  lesion  of  surrounding  parts,  and  connection  of  venous  terminals 
with  septic  or  gangrenous  foci. 

Vascular  thromboses  due  to  general  causes  are,  in  the  great  majority  of 
cases,  situated  in  veins ;  and  to  this  group  the  chief  medical  interest  attaches. 
In  special  characters  of  the  venous  circulation  we  must  seek  the  explanation 
of  the  greater  effectiveness  of  these  general  causes  in  veins  than  in  arteries. 
The  physiological  peculiarities,  partly  general  and  partly  local,  which  come 
especially  into  consideration,  are — the' slower  mean  speed  of  the  blood  in 
veins  than  in  arteries;  the  low  blood-pressure;  the  flow  from  smaller  into 
larger  channels;  the  absence  of  pulsation;  the  presence  of  valves;  fixation 
of  the  venous  wall  in  certain  situation  to  fascise  and  bone;  the  existence  in 
some  places  of  wide  sinuses  and  ampullar  dilatations ;  the  agency  of  certain 
subsidiary  forces,  such  as  muscular  contraction  and  movements  of  the  limbs, 
in  assisting  the  flow  in  the  veins ;  the  composition  of  venous  blood,  particu- 
larly the  higher  content  of  CO^,  and  perhaps  the  functions  of  the  capillaries 
and  small  veins  in  the  production  and  absorption  of  lymph.  It  is  obvious, 
without  detailed  explanation,  that  some  at  least  of  these  special  characters 
must  render  the  venous  system  much  more  favourable  than  the  arterial  to 
the  occurrence,  under  the  general  conditions  known  to  dispose  to  thrombosis, 
of  retardation  of  tlie  blood-current;  eddying  motion  of  the  blood,  and 
damage  to  the  vascular  wall  from  impoverished  and  insufficient  blood-supply, 
or  prolonged  contact  with  micro-organisms  and  toxic  substances,  the  agency 
of  which  in  the  etiology  of  thrombosis  has  already  been  considered. 

The  best  evidence  that  these  mechanical  conditions  determine  the  localisa- 
tion of  the  majority  of  thrombi  of  infective,  anajmic,  and  cachectic  diseases 


THROMBOSIS  137 

is  afforded  by  the  marked  preference  of  such  thrombi  for  situations  where 
these  conditions  are  in  the  highest  degree  operative.  The  tendency  of 
venous  thrombi  to  start  from  valvular  pockets  has  already  been  mentioned. 
It  is  important  to  note  that  thrombi  due  to  general  causes,  unlike  those  start- 
ing from  local  septic  foci,  do  not  begin  in  the  rootlets,  but  originate  usually 
in  the  main  venous  trunks  of  a  member.  The  very  large  veins  are  imusual 
primary  seats  of  marantic  thrombi.  Beginning  as  a  rule  in  a  sinus  or 
medium-sized  vein,  the  thrombus  may  grow  centrally  into  large  veins;  as 
from  the  femoral  into  the  iliacs  and  vena  cava,  and  peripherally  into  small 
veins,  not,  however,  generally  reaching  the  smallest  veins.  The  favourite 
starting-point  of  so-called  marantic  thromboses  of  the  cerebral  sinuses  is  in 
the  middle  of  tlie  superior  longitudinal  sinus  at  the  top  of  the  cranial  cavity, 
whence  the  thrombus  may  extend  forward,  but  tends  especially  to  grow 
toward  the  torcular  Herophili,  and  into  other  sinuses  and  into  the  cerebral 
veins.  There  is,  however,  no  rigid  rule  in  this  matter.  The  plug  may  begin 
in  other  sinuses,  or  even  in  the  cerebral  veins. 

In  extensive  thromboses,  such  as  occur  especially  in  veins  of  the  thigh 
and  leg,  it  is  sometimes  difficult  to  determine  the  point  of  origin  of  the 
thrombus,  and  the  exact  manner  of  its  propagation.  Often,  however,  decisive 
information  can  be  gained  by  careful  attention  to  features  indicative  of  the 
age  of  thrombi,  as  already  described  (p.  119).  Thus  the  autochthonous 
part  of  the  thrombus  is  gray,  or  reddish  gray,  and  firmly  adherent ;  the  con- 
tinued part  often  red  and  more  loosely  attached,  and  the  older  parts  fre- 
quently softened  or  liquefied  in  the  centre.  By  observation  of  such  points  as 
these,  the  common  assumption  that  a  thrombus,  occupying  continuously 
both  large  and  small  veins,  began  in  the  most  distal  veins  and  grew  thence 
into  the  larger  channels,  can  often  be  shown  to  be  erroneous.  An  occluding 
thrombus  may  lead  to  such  disturbances  of  the  circulation  as  to  cause  tlie 
formation  of  discontinuous  multiple  thrombi  on  both  the  central  and  the 
peripheral  sides,  and  these  may  become  connected  by  red  or  mixed  thrombi. 
In  short,  the  modes  of  extension  of  thrombi  are  sometimes  complicated,  and 
not  readily  unravelled. 

The  so-called  law  of  Lancereaux  was  enunciated  by  him  in  1862  as  an 
explanation  of  the  common  site  of  thrombi  in  the  cerebral  sinuses,  and  at  the 
summits  rather  than  at  the  peripheries  of  the  extremities;  his  rule  is  as 
follows : — "  Marantic  thromboses  are  always  formed  at  the  level  of  the  points 
where  the  blood  has  the  greatest  tendency  to  stasis,  that  is,  at  the  limit  of 
the  action  of  tlie  forces  of  cardiac  propulsion  and  of  thoracic  aspiration." 
There  are  serious  physiological  objections  to  the  physical  conceptions  of  the 
circulation  underlying  tliis  so-called  law,  which  in  any  event  cannot  be 
accepted  in  the  exclusive  form  given  to  it  by  Lancereaux.  Wertheimer  has 
12 


138  THROMBOSIS 

shown  that  the  effect  of  thoracic  aspiration  upon  the  venous  circulation  ex- 
tends to  remote  parts  of  the  saphenous  vein  by  the  side  of  the  tendo  AchiUis. 
As  the  collective  sectional  area  of  the  veins  steadily  diminishes  from  the 
capillaries  to  the  heart,  the  average  speed  of  the  blood  must  be  greater  in 
the  large  veins  than  in  the  small  ones,  if  the  circulation  is  to  continue  for 
any  length  of  time ;  and  tliis  remains  true  even  when  the  energy  of  the  blood- 
current  is  feeble. 

^luch  more  satisfactory,  it  seems  tx)  me,  is  tlie  explanation  offered  by  von 
Eecklinghausen,  of  which  mention  has  already  been  made  (p.  133),  This 
explanation  places  the  chief  emphasis  upon  the  eddying  movement  (Wirbel- 
bewegung)  of  the  outer  lines  of  flow  of  the  blood-stream  when  there  are 
counter-currents,  or  when  the  blood  with  retarded  flow  passes  from  smaller 
into  larger  channels  or  over  obstructions,  or  especially  into  spaces  relatively 
too  wide  for  the  received  volimie  of  fluid.  Especially  favourable  for  the 
appearance  of  this  irregularity  of  the  circulation  are  the  ampullar  dilata- 
tions just  above  the  insertion  of  the  venous  valves,  the  intracranial  sinuses, 
and  the  femoral  vein  near  Poupart's  ligament,  which,  in  consequence  of  fixa- 
tion to  bone  or  fasciae,  cannot  readily  adjust  themselves  to  a  lessened  volume 
of  blood,  and  in  which  counter-currents  are  set  up  by  the  obtuse  or  right 
angles  at  which  blood  is  received  from  some  of  the  tributary  veins.  The 
trabeculse  which  cross  tlie  cerebral  sinuses  may  be  a  contributory  factor. 
Similar  irregularities  of  the  blood-flow  must  occur  with  feeble  circulation 
in  other  situations,  as  in  the  pelvic  venous  plexuses,  where  wide  channels 
are  intercalated  between  smaller  ones,  in  the  recesses  of  the  heart,  and  in 
aneur}'sms  and  varicose  veins.  Von  Recklinghausen  has  pointed  out  that 
the  plexus-like  arrangement,  the  entrance  of  small  veins  into  large  ones, 
and  the  close  apposition  of  artery  and  vein  render  branches  of  the  renal  veins 
in  the  kidney  susceptible  to  irregular  blood-currents. 

The  greater  frequency  of  venous  thrombosis  in  the  left  leg  than  in  the 
right  is  attributable  to  the  more  difficult  return-flow  from  the  former,  in 
consequence  of  the  greater  length  and  obliquity  of  tlie  left  common  iliac  vein 
and  its  passage  beneath  the  right  common  iliac  artery.  It  has  been  suggested 
that  pressure  upon  this  vein  by  a  distended  sigmoid  flexure  or  rectum  may 
likewise  contribute  to  slowing  of  the  blood-cujrent  upon  this  side.  The  pre- 
ponderence  of  thromboses  of  the  left  axillary  and  branchial  veins  over  those 
of  the  right  is  attributed  in  a  similar  way  by  Parmentier;  that  is,  to  the 
greater  length  and  obliquitv'  of  the  left  innominate  vein. 

As  has  already  been  urged,  these  mechanical  disturbances  of  the  circulation 
are  not,  by  themselves  alone,  efficient  causes  of  thrombosis.  They  simply 
make  certain  parts  of  tlie  vascular  system  seats  of  election  for  thrombi.  It 
is  quite  possible  to  exaggerate  their  function  in  the  etiology  of  thrombosis. 


THROMBOSIS  139 

The  presence  of  micro-organisms  or  other  changes  in  the  blood  may  induce 
lesions  of  the  vascular  wall  in  any  part  of  the  circulatory  system;  and 
primary  thrombi  may  be  formed  in  situations  apparently  the  most  unpromis- 
ing, so  far  as  the  circulatory  conditions  are  concerned;  as  for  instances  in 
the  pulmonary  veins  and  in  the  venje  cavae  near  the  heart. 

Capillary  Thrombi. — The  blood  in  the  capillaries  remains  fluid,  even 
Math  extensive  venous  and  arterial  thrombosis,  unless  necrosis  or  gangrene 
of  the  tissue  ensue,  in  which  case,  as  in  infarctions,  the  capillaries  are  always 
plugged.  The  interesting  fibrinous  and  hyaline  thromboses  of  the  capillaries 
have  already  been  considered  (pp.  115  and  116). 

Cardiac  Thrombi. — There  is  no  stranger  chapter  in  the  history  of  path- 
ology than  tlie  story  of  cardiac  polypi,  from  the  first  observation  of  fibrinous 
clots  in  the  heart  by  Benivieni,  in  the  fifteenth  century,  until  the  end  of 
the  last  century.  It  is  full  of  warnings  against  the  uncritical  use  of  post- 
mortem findings.  The  cardiac  polyps  of  the  old  vrriters  were,  for  the  most 
part,  nothing  more  than  ordinary  colourless  post-morten  clots.  Nor  has  the 
error  of  confounding  these  with  genuine  thrombi  wholly  disappeared  from 
medical  literature  even  at  the  present  day.  These  moist,  pale,  yellowish, 
smooth,  elastic,  uniform,  more  or  less  translucent,  fibrinous  clots,  softer  or 
firmer  according  to  their  content  of  serum,  non-adherent  though  entangled 
with  muscular  columns  and  trabecule,  often  showing  moulds  of  the  valves 
or  other  projecting  surfaces  vrith,  at  least,  some  red  cruor  clot  at  their  most 
dependent  parts — such  clots,  membranous,  polypoid,  band-like,  or  filling  the 
right  cavities  of  tlie  heart  and  sending  worm-Hke  offshoots  into  the  vessels, 
should  never  be  mistaken  for  the  drier,  opaque,  gray  or  reddish  gray,  granu- 
lar, more  friable,  usually  much  smaller,  adlierent,  often  centrally  softened 
or  stratified  thrombi. 

Although  there  is  a  common  impression  that  these  fibrinous  clots  are 
found  during  the  death  agony,  I  know  of  no  good  reason  for  such  a  view. 
It  is  much  more  probable  that  they  are  analogous  to  the  huffy  coat  of  clots  in 
shed  blood,  and  are  formed  after  death,  when  coagulation  does  not  set  in 
until  the  red  corpuscles  have  settled  from  the  plasma.  Liberation  of  fibrin- 
ferment,  fibrin-content  of  the  blood,  sedimentation-time  of  red  corpuscles 
and  coagulation-time,'  all  variable  elements,  are  the  leading  factors  which 

■■  By  "  fibrin-content "  is  meant  the  amount  of  fibrin  yielded  by  the  blood,  and 
is  not  of  course  to  be  understood  as  implying  the  pre-existence  of  fibrin  in  the 
blood.  The  rapidity  of  coagulation  is  an  element  which  is  more  or  less  inde- 
pendent of  the  total  yield  of  fibrin.  Red  corpuscles  settle  from  plasma  or  from 
serum  with  varying  degrees  of  rapidity  in  different  specimens  of  blood.  Clots 
also  vary  much  as  to  their  contraction  and  the  separation  of  serum.  Although 
in  using  such  an  expression  as  "  coagulability  of  the  blood  "  these  factors  are 
often  confounded,  it  is  important  that  they  should  be  distinguished. 


140  THROAIBOSIS 

determine  the  production  of  these  colourless  clots.  Most  striking  examples 
of  colourless  clots  are  foimd  after  deatli  from  pneumonia  and  acute  articular 
rheumatism,  where  the  fibrin-content  is  high,  the  sedimentation-time  rapid, 
and  the  coagulation-time  slow.  The  whole  doctrine  of  death  from  "  heart- 
clot"  in  these  and  other  acute  diseases  is  based,  in  my  opinion,  upon  mis- 
taken interpretation  of  fibrinous  post-mortem  clots. 

The  fresh  vegetations  of  endocarditis  are  not  generally  included  in  the 
consideration  of  cardiac  thrombi.  Still  they  are  genuine  thrombi,  and  there 
is  no  more  favourable  situation  for  the  study  of  the  formation  of  mycotic 
thrombi  than  the  acutely  inflamed  heart-valve.  The  first  step  is  the  inva- 
sion of  bacteria,  as  a  rule  directly  from  the  blood  in  the  cardiac  cavities,  into 
the  endothelial  and  subendothlial  layers.  The  surrounding  cells  undergo 
rapid  necrosis  with  karyorrhexis ;  and  simultaneously  are  deposited  upon 
the  damaged  spot  masses  of  conglutinated  platelets  followed  by  leucocytes 
and  fibrin,  these  masses  forming  the  vegetations.  Proliferation  of  the 
subendothelial  and  adjacent  cells  quickly  follows,  pol}Tiuclear  leucocytes 
migrate  into  the  area,  and  before  long  new  vessels  with  organisation  of  the 
thrombus  make  their  appearance.  A  process  essentially  the  same  may 
occur  not  only  in  the  mural  endocardium  but  also  in  arteries  and  veins 
(vegetative  arteritis,  vegetative  phlebitis,  p.  128). 

Putting  aside  these  endocardial  vegetations,  it  has  been  customary  to 
consider  the  conditions  leading  to  cardiac  tiirombosis  as  essentially  identical 
with  those  of  peripheral  venous  thrombsis,  but  there  are  differences.  Cardiac 
thrombi  are  found  especially  in  association  with  chronic  diseases  of  the  heart, 
lungs,  arteries,  and  kidneys;  in  all  of  which,  with  the  exception  of  pul- 
monar}'  tuberculosis,  peripheral  venous  thrombosis  is  uncommon.  On  the 
other  hand,  most  of  the  acute  infective  diseases,  as  enteric  fever,  influenza, 
pneumonia,  which  are  so  important  in  the  etiology  of  venous  thrombosis,  are 
in  general  of  less  relative  importance  in  the  causation  of  cardiac  thrombosis, 
although  it  may  occur  in  these  diseases.  In  cachectic  states,  especially 
phthisis  and  cancer,  the  conditions  as  regards  the  incidence  of  cardiac  and 
of  venous  thrombi  are  more  nearly  identical,  for  here  thrombi  are  often 
enough  found  in  the  heart;  particularly  when  there  is  well-marked  fatty 
degeneration.  Cardiac  thrombosis  stands  in  no  such  peculiar  relation  to 
chlorosis  and  gout  as  does  venous  thrombosis,  although  its  occurrence  in 
these  diseases  is  not  unknown.  Tiie  great  field  for  cardiac  thrombi  is 
afforded  by  diseases  of  the  valves  and  walls  of  the  heart,  and  especially  by 
dilatation  of  one  or  more  of  its  cavities  with  cardiac  insufficiency  (asystole 
of  the  French  school)  ;  conditions  which,  in  spite  of  the  great  retardation 
of  the  venous  flow,  are  not  often  attended  by  peripheral  venous  thrombosis, 
unless  in  association  with  diseases  known  to  dispose  to  the  latter. 


THROMBOSIS  141 

The  seats  of  election  for  cardiac  thrombi  are  the  auricular  appendices  and 
the  ventricular  apices  between  the  coluninae  cameae ;  the  particular  situation 
varying  as  the  cause  may  affect  the  whole  heart,  on  only  one  side,  or  one 
cavity.  In  cardiac  insufficiency  from  general  or  local  causes  these  recesses 
and  pockets  must  offer  the  best  possible  conditions  for  slowing  of  the  blood- 
current,  and  especially  for  the  formation  of  eddies.  That  there  is  no  actual 
stasis  of  the  blood  is  shown  by  the  gray  or  reddish  gray  colour  of  the  thrombi. 

The  familiar  globular  thrombi  (vegetations  globuleuses,  of  Laennec) 
are  by  far  the  commonest  form  of  cardiac  tlirombus.  Varying  in  size  usually 
from  a  pea  to  a  hazel-nut  they  may  attain  the  size  of  a  hen's  egg.  They  are 
usually  multiple,  and  neighbouring  ones  are  connected  by  an  adherent  sub- 
trabecular  thrombotic  meshwork  or  membrane,  of  which  they  constitute 
sessile  or  pedunculated  spheroidal  or  ovoid  projections.  Their  surface 
may  be  smooth,  or  marked  by  delicate  lines  or  ribs;  and  their  interior  is 
usually  converted  into  an  opaque,  gray,  or  brownish  red  grumous  fluid, 
80  that  the  whole  resembles  a  cyst  with  puriform  contents.  The  liquefaction 
is  of  the  bland  variety  already  described  (p.  120).  Although  the  projecting 
covering  of  these  cysts  is  often  only  a  thin  shell  it  rarely  bursts.  These 
thrombi  may,  however,  be  the  source  of  emboli.  Hearts  containing  these 
thrombi  are  often  the  seat  of  fatty  degeneration.  Usually  no  localised 
mural  disease  is  to  be  detected  with  the  naked  eye  beneath  these  thrombi, 
although  the  microscope  generally  shows  degeneration  or  defect  of  the 
endothelium.  It  is  most  exceptional  for  any  trace  of  organisation  to  be 
present  in  these  globular  thrombi. 

Calcifieation  of  cardiac  thrombi  is  a  rare  event.  Delepine  has  described 
very  fully  a  cardiolith,  and  has  collected  reports  of  similar  cases.  Some 
of  these  are  probably  phleboliths  in  or  derived  from  varicose  veins  which 
Wagner,  Zahn,  and  Bostroem  have  described  in  the  wall  of  the  heart,  par- 
ticularly in  the  septum  auriculorum. 

Somewhat  different  as  a  rule  are  the  mural  thrombi  found  on  areas  of 
circumscribed  disease  of  the  heart  wall;  as  on  infarction,  fibroid  patches," 
and  gummata,  and  in  partial  aneurysm.  These  may  be  identical  in  appear- 
ance with  the  ordinary  globular  cysts ;  but  often  they  are  flat  or  polypoid, 
stratified,  and  more  intimately  incorporated  with  the  cardiac  wall. 

Cardiac  thrombi  may  be  in  the  shape  of  massive  or  of  elongated  polypoid 
formations,  occupying  a  large  part  of  one  of  the  cavities,  and  extending 

^  It  is  interesting  to  note  that  in  1809,  Allan  Burns  in  his  classical  work  on 
"  Diseases  of  the  Heart,"  in  recording  his  observations  on  angina  pectoris  with 
calcification  of  the  coronary  arteries  and  polypi  in  the  left  ventricle,  called 
attention  to  the  relations  between  disease  of  the  coronary  arteries  and  cardiac 
thrombosis.  He  thus  anticipated  Weber  and  Deguy,  and  other  recent  writers, 
who  have  emphasised  the  occurrence  of  cardiac  thrombi  in  angio-sclerotic  hearts. 


142  THROMBOSIS 

even  through  valvular  orifices  into  adjacent  cavities  or  vessels.  One  of  the 
cavities,  usually  a  dilated  auricle,  may  be  nearly  filled  with  a  massive  lami- 
nated thrombus,  as  in  a  case  reported  by  Osier  which  I  examined.  There  is 
much  resemblance  between  the  clot  in  these  cases  and  that  found  in  aneu- 
rysms. 

Apart  from  endocardial  vegetations  not  much  is  known  of  infective 
tkrouihi  in  the  heart,  although  it  is  probable  that  they  occur  more  fre- 
quently than  is  suspected.  In  a  child  dead  of  scarlatina  I  found,  in  associa- 
tion with  streptococcal  mitral  endocarditis,  softened  thrombi  containing 
streptococci  in  the  right  auricular  appendix.  There  are  a  few  scattered 
reports  of  the  discover}^  of  bacteria  in  cardiac  thrombi.  Particularly  inter- 
esting are  the  observations  of  Weichselbaum,  of  Birch-Hirschfeld,  and  of 
Kotlar,  of  tubercle  bacilli  in  white  cardiac  thrombi.  Birch-Hirschfeld 
found  in  a  case  of  extensive  genito-urinary  and  chronic  pulmonar)'  tuber- 
culosis a  white  organised  thrombus  in  the  appendix  of  the  right  auricle 
which  contained  many  tubercle  bacilli  and  numerous  tubercles.  In  these 
and  similar  cases  there  is  difficulty  in  determining  whether  the  bacteria  are 
the  direct  cause  of  the  thrombosis,  or  are  secondary  invaders.  Kotlar 
interprets  his  case  as  the  development  of  miliary  tubercles  in  an  organised 
thrombus. 

As  there  are  unquestionable  instances  of  finding  emboli  derived  from 
venous  thrombi  in  the  right  heart,  the  possibility  of  a  thrombus  arising 
secondarily  from  such  an  embolus  in  this  situation  may  be  admitted;  but  I 
know  of  no  convincing  example. 

Ball-thrombi,  loose  in  the  left  auricle,  are  rare  forms  of  cardiac  thrombi. 
The  first  observation  which  I  have  found  of  such  a  thrombus  was  published 
by  William  Wood  in  1814,  in  Edinburgh.  As  in  other  typical  cases,  the 
loose  thrombus  was  in  the  left  auricle  and  there  was  extreme  mitral  stenosis. 
The  patient,  a  girl  15  years  old,  had  the  regular  symptoms  of  chronic  val- 
vular disease.  Death  was  not  sudden.  Wood  thus  describes  the  appearances : 
"  The  substance  occupying  the  sinus  venosus  of  the  left  auricle,  when  par- 
ticularly examined,  was  found  to  be  of  a  darkish  red  colour,  in  form  com- 
pletely spherical,  measuring  rather  more  than  an  inch  and  a  half  in  diameter. 
It  felt  firm,  but  elastic;  the  surface  was  ever}'whcre  smooth  and  polished, 
but  having  a  singularly  clotted  appearance.  Rolling  loosely  in  the  auricle, 
it  had  no  connection  with  surrounding  parts.  When  cut  open,  after  having 
been  kept  for  some  days  in  diluted  alcohol,  it  was  found  to  consist  of  a  sac, 
one-eighth  of  an  inch  in  thickness,  formed  of  an  immense  number  of  firm, 
smooth  lamina?,  which  could  be  easily  separated  from  each  other.  Within 
the  cavity  formed  by  this  sac  was  contained  a  quantity  of  coagulated  blood." 
Adherent  to  the  wall  of  the  auricle  near  the  mitral  valve  was  a  firm,  oval 


THROMBOSIS  143 

thrombus  on  the  free  surface  of  which  was  a  superficial  concavity  which 
formed  a  "  kind  of  socket  for  the  loose  ball  to  roll  in."  This  last  feature 
is  a  unique  observation. 

In  1863,  Dr.  J.  W.  Ogle  reported  a  typical  instance  of  ball-thrombus  in 
the  left  auricle  with  extreme  mitral  stenosis,  and  accompanied  the  report 
with  an  admirable  drawing.  In  1877  Dr.  Wickham  Legg  reported  likewise, 
to  the  London  Pathological  Society,  two  cases  of  ball-thrombi  in  the  left 
auricle  with  mitral  stenosis.  He  refers  to  Ogle's  specimen  which  he 
re-examined,  and  to  a  fourth  specimen  in  the  museum  of  St.  Thomas's  Hospi- 
tal. One  of  his  cases  is  unique  in  the  presence  of  two  ball-thrombi  in  the 
left  auricle.  This  patient  was  brought  dead  to  the  hospital,  and  presumably 
died  suddenly  in  the  street.  Von  Recklinghausen's  brief  description,  in 
1883,  of  two  cases  of  ball-thrombi  is  quoted  in  the  subsequent  German 
records  on  the  subject  as  the  first  observation  of  this  interesting  form  of 
cardiac  thrombus;  although  there  were  much  fuller  previous  accounts  of 
at  least  four  cases,  with  mention  of  a  fifth,  in  Scotch  and  English  records 
extending  back  as  far  as  1814;  those  of  Ogle  and  Legg  being  certainly  very 
accessible  in  the  "  Transactions  of  the  London  Pathological  Society."  Mac- 
leod's  case  of  loose  thrombus  in  the  right  auricle  is  properly  excluded  by  von 
Recklinghausen  from  the  class  of  ball-thrombi.  If  the  conception  of  a  ball- 
thrombus  be  simply  that  of  a  loose  thrombus  too  large  to  pass  through  the 
valvular  orifice,  then  van  der  Byl's  case,  reported  in  1858,  should  be  included 
in  this  class.  He  found  in  a  case  of  sudden  death  "  an  irregular,  shaggy- 
looking  mass  sticking"  in  the  extremely  contracted  mitral  orifice.  When 
floated  out  in  water  this  assumed  a  sac-like  appearance,  was  about  the  size 
of  a  pigeon's  egg,  and  completed  a  broken  thrombotic  sac  in  the  auricular 
appendix.  This  embolus  must  have  been  freshly  detached,  and  had  not 
assumed  the  typical  spherical  or  ovoid  shape  of  the  ball-thrombus.  There 
have  been  later  reports  of  ball-thrombi,  by  Hertz  (two  cases).  Osier  (two 
cases),  Arnold,  von  Ziemssen,  Redtenbacher,  Krumbholz,  Rosenbach,  Stange, 
and  Eichhorst  (three  cases  mentioned  without  any  details),  making  twenty, 
without  including  Macleod's  and  van  der  Byl's  cases."  Of  these,  fifteen  are 
reported  with  sufficient  details  for  analysis.  This  form  of  thrombus,  there- 
fore, although  rare,  is  not  so  much  of  a  curiosity  as  has  been  generally 
supposed. 

"  I  have  also  not  included  Schmorl's  case,  mentioned  by  Stange,  as  it  is  evidently 
identical  with  that  of  Krumbholz,  nor  Fiirbringer's  case  of  numerous  globular 
thrombi,  the  largest  the  size  of  a  cherry,  in  the  right  auricle,  although  he  reports 
it  as  belonging  to  the  group  of  ball-thrombi.  He  is  evidently  under  a  misconcep- 
tion of  the  nature  of  ball-thrombi.  There  was  not  the  slightest  reason  why  these 
small  bodies,  many  of  them  indeed  minute,  if  they  were  really  loose  during  life, 
should  not  have  travelled  on  with  the  blood-stream. 


144  THROMBOSIS 

Three  characters,  in  my  opinion,  should  enter  into  the  definition  of  a 
ball-thrombus:  (i.)  entire  absence  of  attachment  and  consequent  free 
mobility;  (ii.)  imprisonment  in  consquence  of  excess  in  the  diameter  of 
tlie  thrombus  over  that  of  the  first  narrowing  in  the  circulatory  passage 
ahead  of  it;  and  (iii.)  such  c-onsistence  and  shape  that  the  thrombus  must 
not  of  necessity  lodge  as  an  embolus  in  this  passage.  The  third  point  does 
not  prejudice  the  question  of  the  possibility  of  ball-thrombus  lodging  as  an 
embolus ;  but  it  excludes  from  the  group  such  detached,  shaggy,  irregular 
masses  (as  in  van  der  Byl's  case)  as  must  necessarily  be  caught  at  once  as 
emboli  in  the  narrowed  passage  in  front.  According  to  this  definition  a 
ball-thrombus  might,  theoretically  at  least,  occur  in  any  circumscribed  or 
sac-like  dilatation  of  the  circulatory  system;  indeed  von  Eecklinghausen 
considers  loose  phleboliths  and  cardiac  ball-thrombi  as  analogous. 

All  of  the  cardiac  ball-thrombi — as  thus  defined — hitherto  reported,  were 
in  the  dilated  left  auricle;  and,  with  one  exception,  were  associated  with 
mitral  stenosis.  In  Stange's  case  there  was  aortic  stenosis,  with  slight 
insufficiency  of  the  mitral  valve  without-  stenosis.  The  agency  of  mitral 
stenosis  in  the  production  of  ball-thrombi  is  not  only  that  it  prevents  the 
escape  of  detached  thrombi  which  might  pass  the  normal  orifice,  but  also 
that  it  favours  the  formation  of  thrombi  in  the  left  auricle,  particularly  in 
the  appendix ;  and  doubtless  also,  through  the  particular  disturbance  of  the 
circulation,  aids  in  their  detachment,  increases  the  tendency  to  their  rotary 
motion,  and  prevents  the  co;nplete  emptying  of  the  left  auricle  during 
systole,  thus  rendering  more  difficult  the  lodgment  and  fixation  in  the  val- 
vular orifice  of  thrombotic  masses  which  at  first  may  be  irregular  in  shape. 

The  thrombi  have  varied  in  size  from  that  of  a  small  walnut  to  tliat  of  a 
hen's  egg;  in  Wood's  case  the  thrombus  was  over  an  inch  and  a  half  in 
diameter,  and  in  Ogle's  the  weight  was  more  than  four  drachms.  In  ten  the 
shape  was  spherical;  in  four  ovoid;  in  one  (probably  of  recent  separation) 
a  somewhat  irregular  flattened  hemisphere.  In  six  the  surface  was  smooth 
and  polished;  in  six  marked  by  granules,  lines,  ribs,  or  little  depressions; 
in  two  smooth  and  knobbed;  and  in  one  (Redtenbacher's)  beset  wath  very 
fine,  gray,  fibrinous  villi.  Nine  were  centrally  softened;  four  solid  through- 
out ;  and  for  two  there  is  no  statement  on  this  point.  The  colour  was  gray 
or  reddish  gray;  in  Wood's  "darkish  red."  In  the  majority  of  cases  it  is 
said  there  were  adherent  thrombi  in  the  left  auricle,  usually  the  appendix ; 
and  where  this  is  not  expressly  stated  they  may  have  been  present.  In  five 
cases  only  was  tbere  a  rough  or  projecting  spot  on  the  surface  of  the  ball 
indicative  of  the  previous  attachment;  and  in  two  this  spot  was  not  at  all 
smoothed  off:  so  that  the  detachment  was  evidently  very  recent,  possibly 
mdeed  during  the  autopsy,  as  in  one  of  tlie  two  loose  balls  in  Legg's  first 


THEOMBOSIS  145 

case.  Krumbholz  says  that  tlie  surface  of  his  thrombus  was  covered  with 
endothelium.  In  none,  however,  was  any  distinct  evidence  of  organisation 
detected,  for  von  Ziemssen's  statement  on  this  point  is  too  indefinite  to  be 
considered. 

Ogle,  in  1863,  clearly  recognised  the  mode  of  production  of  a  ball-throm- 
bus "  by  the  constant  and  free  agitation  of  a  fragment  of  fibrinous  coagulum 
separated  from  some  part  of  the  endocardium,  and  uniformly  increased  by 
fresh  material  at  its  circumference  precipitated  from  the  surrounding  blood- 
stream." Von  Recklinghausen  has  given-  the  fullest  and  most  satisfactory 
explanation  of  the  spherical  shape  and  smooth  surface,  in  noting  tliat  at 
least  some  ball-thrombi  have  a  globular  shape  when  first  detached;  and  that 
irregular  bodies,  of  the  consistence  of  thrombi,  rotating  in  a  cavity  and  grow- 
ing by  successive  accretions,  assume  a  spherical  shape  by  a  process  of  mould- 
ing, and  not  by  the  grinding  or  breaking  off  of  corners  and  projections,  as  was 
suggested  by  Hertz  to  account  for  the  smooth  roundness  of  ball-thrombi. 
In  two  or  three  instances  where  the  ball-thrombus  has  consisted  of  a  central 
irregular  nucleus  envoloped  in  a  concentrically  laminated  capsule,  it  has 
been  assumed  that  the  former  represents  tlie  original  detached  part,  and  the 
latter  successive  accretions  during  free  rotations  in  the  auricle.  While  sug- 
gestive of  such  an  interpretation,  this  structure  may,  however,  exist  in  still 
adherent  globular  thrombi.  It  seems  to  me  probable  that  most  ball-thrombi 
are  smooth  and  at  least  approximately  spherical  when  first  detached.  It  is 
difficult  to  say  how  much  a  thrombus  may  have  grown  after  its  separation. 

In  nearly  all  cases  that  the  loose  thrombus  apparently  came  from  the  left 
auricular  appendix,  where  adherent  thrombi  were  rarely  missed  when  it  is 
expressly  stated  that  they  were  searched  for.  In  Wood's  case  the  dark  red 
colour,  central  blood-clot,  and  polished  surface  suggest  the  possibility  tliat 
the  loose  body  was  a  separated  polypus  resulting  from  haemorrhage  in  the 
wall  of  the  auricle  or  from  a  varix ;  and  this  opinion  is  strengthened  by  the 
socket-like  depression  in  the  adherent  thrombus,  for  it  is  not  clear  how  such 
a  socket  could  be  formed  by  a  thrombus  loose  in  the  auricle ;  but  it  might 
have  been  the  impression  left  by  a  polypus  attached  at  some  other  point. 

As  regards  the  clinical  significance '  of  cardiac  ball-thrombi,  Wickham 
Legg  expressed  the  notion  which  would  probably  at  first  occur  to  most 
persons.  "  A  loose  thrombus,"  he  says,  "  in  the  left  auricle  would  at  any 
time  be  ready  to  act  as  a  ball-valve,  and  stop  the  circulation  in  the  mitral 
orifice  ";  and  in  this  opinion  he  was  strengthened  by  the  presimiably  sudden 
death  of  his  patient.    Von  Eecklinghausen,  however,  who  at  the  time  knew 

'  In  order  to  complete  without  interruption  tlie  description  of  ball-thrombi  I 
introduce  here  their  clinical  significance,  although  the  consideration  of  the  symp- 
toms of  thrombosis  is  taken  up  subsequently. 


146  THROMBOSIS 

only  of  his  owa  two  cases  and  the  two  of  Hertz,  in  critising  a  similar  opinion 
expressed  by  the  latter,  brought  forward  several  arguments  opposed  to  tliis 
notion.  The  main  points  of  his  argument  are  that  instances  of  sudden  death 
are  not  infrequent  in  extreme  mitral  stenosis  without  ball-tlirombi ;  that 
lodgment  of  the  thrombus  in  the  mitral  orifice  has  not  been  observed,  and, 
even  if  it  were  found  lying  loosely  over  the  orifice  at  the  autopsy,  that  this 
would  not  indicate  its  position  at  tlie  moment  of  death ;  that  the  funnel  of 
the  stenosed  mitral  orifice  is  elliptical  in  cross-section  and  shallow,  so  that 
a  rolling  sphere  of  the  consistence  of  a  ball-thrombus  could  neither  com- 
pletely occlude  it  nor  get  wedged  in  it,  nor,  if  the  ball  should  enter  the  shallow 
funnel,  is  tliere  anything  to  hold  it  there,  so  that  the  next  moment  it  would 
roll  out.  To  these  points  may  be  added  Arnold's  argument  that  the  throm- 
bus cannot  be  horizontally  pressed  by  the  auricular  contractions  against  the 
orifice;  for  during  its  systole  the  dilated  auricle  does  not  completely  empty 
itself  of  blood  through  the  stenosed  orifice. 

The  histories  of  the  cases  of  cardiac  ball-thrombus  support  in  general  the 
position  of  von  Recklinghausen,  No  symptoms  were  observed  which  may 
not  occur  in  mitral  stenosis.  Death  was  gradual  in  all  except  four.  In 
only  one  of  these  four  cases  of  sudden  death  was  tliere  any  conclusive  evi- 
dence that  the  thrombus  was  the  cause.  This  was  Dr.  Osier's  second  patient 
upon  whom  the  autopsy  was  made  in  my  laboratory  by  Dr.  Flexner.  The 
patient,  a  woman  aged  20,  was  seen  in  good  condition  a  few  hours  before 
death.  At  4.30  a.  m.  she  was  found  by  the  nurse  very  cyanotic,  she  gave  a 
gasp  or  two,  and  died  in  a  few  moments.  At  the  autopsy  were  found  marked 
hypertrophy  and  dilatation  of  the  left  auricle,  right  ventricle,  and  to  a  less 
extent  right  auricle;  without  dilatation  or  hypertrophy  of  the  left  ventricle. 
The  segments  of  the  mitral  valve  were  thickened,  adherent,  and  drawn  down 
by  great  shortening  of  the  chordae  tendinege,  so  as  to  form  the  wall  of  a  dis- 
tinct funnel.  There  were  no  fresh  vegetations  and  no  oedema.  The  stenosis 
was  not  extreme,  the  mitral  orifice  readily  admitting  the  index  finger.  The 
other  valves  and  the  coronary  arteries  were  normal.  An  ovoid  ball-thrombus, 
resembling  a  thick  chestnut,  measuring  4x3.5x3  ctm.,  was  found,  upon 
opening  tlie  heart,  occupying  with  its  smaller  end  and  completely  blocking 
the  funnel-shaped  mitral  orifice,  from  which  it  was  readily  removed  l)y  the 
fingers.  At  one  pole  of  the  thrombus  was  an  irregular,  roughened  spot 
indicating  a  former  attachment,  probably  to  a  thrombus  in  the  appendix. 
There  can  be  no  reasonable  doubt  that  the  thrombus  in  this  case  was  the 
cause  of  the  sudden  death,  which  is  certainly  not  a  conmion  occurrence  with 
such  moderate  uncomplicated  mitral  stenosis  at  the  age  of  this  patient.  In- 
deed sudden  death  is  less  common  in  uncomplicated  mitral  stenosis  than  in 
aortic  valvular  disease;  as  the  former  occurs  often  in  young  women,  and  is 


THKOMBOSIS  147 

usually  unassociated  with  disease  of  the  coronary  arteries.  In  the  tliree 
other  instances  of  sudden  death  with  ball-thrombus  the  ages  were  21,  23, 
and  39  years  respectively.  Only  in  one  of  tliese  was  the  thrombus  a  perfect 
sphere ;  so  that  it  would  appear  that  an  oval  thrombus  is  more  likely  to  plug 
the  mitral  orifice  than  a  spherical  one.  This  view  is  strengthened  by  the  fact 
that  of  the  four  observations  of  ovoid  thrombi  in  tliree  death  was  sudden. 
In  the  light  of  our  case  it  seems  clear  that  a  ball-thrombus  may  "  act  as  a 
ball-valve  and  stop  the  circulation  in  the  mitral  orifice,^'  as  suggested  by 
Legg ;  but  it  is  certain  that  tliis  is  an  exceptional  occurrence. 

Under  the  name  of  cardiac  pedunculated  polyps  various  formations  have 
been  described.  Some  of  these  are  ordinary  unorganised  or  partly  organised 
polypoid  thrombi,  about  which  nothing  more  need  be  said ;  but  others  are  very 
remarkable  structures  which  occupy  an  entirely  exceptional  position,  not  only 
among  cardiac  thrombi  but  among  thrombi  in  general.  In  the  older  records 
some  of  the  latter  were  described  as  fibromatous  or  myxomatous  polyps, — 
two  as  hasmatoma;  but  in  the  later  reports  most  have  been  recognised  as 
organised  thrombi.  They  are  often  called  true  polyps  in  distinction  from 
the  false  polyps  of  tlie  older  writers. 

The  literature  of  the  subject  begins  with  Allan  Burns  in  1809.  References 
to  many  of  the  cases  will  be  found  in  the  papers  of  Hertz,  zum  Busch,  and 
Pawlowski.  Among  the  noteworthy  observations  since  Hertz  are  those  of 
Czapek,  Voelcker,  Bostroem,  and  Ewart  and  Rolleston.  I  have  found 
records  of  thirty-three  cases,  at  least  twenty  of  which  were  well-characterised, 
organised,  pedunculated  polyps.  Twenty-five  sprang  from  the  wall  of  the 
left  auricle,  usually  the  septum;  four  from  the  right  auricle;  four  from  the 
left  ventricle. 

The  following  are  the  more  notable  features  of  these  curious  formations : — 
In  many  instances  no  cause  whatever  could  be  found  for  their  occurrence. 
The  hearts  containing  them  were  often  otherwise  entirely  normal,  wath  the 
exception  of  changes  manifestly  secondary  to  the  polyp,  such  as  nodular 
fibroid  thickening  of  the  mitral  segments  and  dilatation  and  hypertrophy 
of  the  left  auricle  and  right  ventricle.  Unlike  other  cardiac  thrombi  they 
are  solitary  formations,  and  often  unassociated  with  ordinary  thrombotic 
deposits.  The  vast  majority  of  these  polyps  spring  from  the  septimi  of  the 
left  auricle  near  the  fossa  ovalis  with  short  pedicle,  sometimes  narrow,  some- 
times broad.  They  are  firm  or  gelatinous,  elastic,  ovoid  or  pear-shaped 
formations,  in  several  instances  hanging  down  into  the  left  ventricle  with  a 
constriction  corresponding  to  the  mitral  orifice.  The  surface  is  usually 
glistening,  smooth,  and  covered  by  a  distinct  membrane  which  often  resem- 
bles tlie  endocardium.  It  may  present  calcific,  atheromatous,  or  pigmented 
patches;  and  upon  it  may  be  irregular  knobs  and  depressions.    The  colour 


148  THROMBOSIS 

is  described  as  yellowish,  gray,  dark  red  or  brownish  red;  the  colour  often 
varying  in  different  parts  of  the  polyp.  A  prevailing  dark  red  colour  has 
been  observed  in  a  large  number  of  tlie  cases.  In  distinction  from  nearly 
all  other  cardiac  thrombi,  these  polyps  are  more  or  less  organised  by  con- 
nective tissue  and  vessels;  the  organisation  in  some  being  little  marked,  in 
others  so  far  advanced  tliat  the  structure  resembles  that  of  a  fibroma  or 
myxoma.  The  central  part  is  often  imorganised  or  less  organised  tlian  the 
base  and  periphery.  In  the  incompletely  organised  forms  the  substance  of 
the  polyp  is  composed  of  red  corpuscles,  fibrin,  granular  detritus,  yellow 
blood-pigment,  leucocytes,  and  other  cells  between  tlie  blood-vessels  and 
fibrous  septa.  Laminated  fibrin  may  be  present  in  the  peripheral  layers. 
Unless  ordinary  thromlti  are  likewise  present,  emboli  are  usually  missed. 
A  further  distinction  from  the  ordinary  cardiac  thrombi  is  that  many  of 
tliese  pol}nps,  by  encroaching  upon  the  mitral  orifice,  are  of  as  much  clinical 
as  anatomical  interest;  the  diagnosis  during  life  in  these  cases  being  mitral 
disease,  usually  stenosis. 

We  have  no  satisfactory  explanation  of  these  pedunculated  polyps.  The 
ordinary  causes  of  thrombosis  are  generally  absent.  Their  commonest  site 
of  origin,  the  septum  of  the  left  auricle  near  the  oval  fossa,  is  not  a  usual 
situation  for  ordinar}'  thrombi.  They  stand  in  no  demonstrable  relation  to 
patency  of  the  foramen  ovale  or  to  circumscribed  endocarditis  in  this  situa- 
tion. 

Bostroem  has  suggested  that  an  explanation  may  be  found  in  the  existence 
of  varicose  veins  which  liave  been  observed  repeatedly  in  the  septum,  usually 
near  the  posterior  quadrant  of  the  foramen  ovale.  A  difficulty  with  this 
explanation  is  that  nine  out  of  ten  of  the  varicosities  observed  by  Wagner, 
Zahn,  Kindfleisck,  and  Bostroem  were  on  the  right  side  of  the  septum.  In 
one  instance,  however,  Bostroem  found  in  the  left  auricle  a  spherical,  dark 
red  polyp,  13  mm.  in  diameter,  attached  by  a  sliort  narrow  stem  to  the  septum 
on  the  posterior  lower  margin  of  the  completely  closed  foramen  ovale.  This 
proved  to  be  a  varix  containing  a  phlebolith.  In  another  case  a  similar 
thrombosed  varix  had  broken  from  its  pedicle  on  the  septum  of  the  right 
auricle,  and  was  lodged  as  an  embolus  in  a  branch  of  the  pulmonary  artery. 
He  suggests  this  as  a  possible  source  of  ball-thrombi.  Of  still  greater  signifi- 
cance is  Bostroem's  demonstration  in  an  old  museum  s])ecimen,  lal)elled 
"  thrombosis  of  the  right  auricle  (pedunculated  cardiac  polyp)  peripherally 
organised,"  of  an  enormous  completely  thrombosed  varix  almost  filling  the 
right  auricle.  In  still  another  case  he  proved  conclusively  tliat  a  broad- 
based,  nearly  spiierical  polyp,  occupying  a  large  part  of  the  right  auricle, 
was  a  ha}morrhage  in  the  wall  of  the  auricle.  Choisy  and  Nuhn  long  ago 
interpreted  the  polj'ps,  which  they  observed,  as  the  result  of  lijemorrhage  in 
the  septum  of  tlie  left  auricle. 


THROMBOSIS  149 

In  the  light  of  Bostroem's  interesting  investigations,  more  attention  than 
has  been  customary  should  be  given  to  the  possibility  that  pedunculated 
polyps  are  the  result  of  ha?morrhage  or  are  thrombosed  varices.  Most  com- 
petent investigators,  however,  have  unhesitatingly  pronounced  the  polyps 
which  they  have  examined  to  be  organised  thrombi.  It  would  appear,  there- 
fore, that  the  nature  of  these  formations  is  not  always  the  same.  At  any 
rate  the  great  majority  of  the  typical  pedunculated  polyps,  to  which  the 
preceding  description  applies,  occupy  a  position  quite  apart  from  ordinary 
cardiac  thrombi.  As  already  remarked,  by  no  means  all  of  the  cases  described 
as  true  cardiac  polyps  belong  to  this  peculiar  group.  Some,  as  in  Krumm's 
case,  are  ordinary  partly  organised  thrombi  attached  to  diseased  patches  of 
the  heart  wall. 

Association  with  Certain  Diseases. — Thromboses  may  be  divided,  as 
regards  their  clinical  relations,  into  the  following  groups:  (i.)  those  result- 
ing from  direct  injury  of  vessels,  including  the  penetration  of  foreign  bodies ; 
(ii.)  referable  to  diseases  of  the  vascular  wall,  as  to  angio-sclerosis,  syphili- 
tic arteritis,  aneurysm,  varix;  (iii.)  caused  by  lesions  of  neighbouring  parts; 
(iv.)  thromboses  of  arteries  and  veins  whose  terminal  branches  end  in 
septic  and  gangrenous  areas;  (v.)  complications  or  sequels  of  (a)  infective 
diseases,  (6)  cachectic  and  anaemic  states,  (c)  cardiac  disease,  (d)  certain 
constitutional  diseases;  (vi.)  idiopathic  and  primary  infective  thromboses. 
Several  of  these  groups,  being  mainly  of  surgical  interest,  will  not  be  con- 
sidered here.  The  thromboses  embraced  in  the  fifth  and  sixth  groups  are 
of  such  special  medical  interest  that  it  is  proper  in  this  article  to  give  them 
particular  attention ;  although  it  is  manifestly  impossible  within  reasonable 
limits  to  take  up  all  in  detail.  Some  of  them  are  noticed  in  other  parts  of 
this  work. 

Enteric  Fever. — Cardiac  Thrombosis  is  a  rare  complication  of  enteric 
fever.  In  2000  fatal  cases  of  enteric  fever  in  Munich  there  were  only  eleven 
instances  of  acute  endocarditis  (Holscher).  Girode,  Viti,  Carbone,  and 
Vincent  have  found  the  typhoid  bacillus  in  endocardial  vegetations;  and 
vegetative  endocarditis  has  been  produced  experimentally  by  intravascular 
injections  of  pure  cultures  of  the  typhoid  organism  combined  with  injury 
to  tlie  valves.  More  frequently,  the  endocarditis  has  been  due  to  secondary 
infection.  In  rare  instances  in  the  course  of  enteric  fever  globular  thrombi 
are  formed  in  the  auricular  appendages  and  ventricular  apices;  and  these, 
as  well  as  the  endocardial  vegetations,  may  be  the  source  of  emboli. 

Arterial  thromhosis  is  a  still  rarer  event,  but,  in  consequence  of  its 
gravity,  an  important  one.  Bettke,  in  1420  cases,  found  four  of  gangrene  of 
the  extremities ;  but  in  2000  Munich  autopsies  no  instance  is  recorded,  a  result 
in  contrast  with  fifty-nine  of  thrombosis  of  the  femoral  vein  in  the  same 


150  THKOMBOSIS 

series.  Keen,  in  his  admirable  monograph,  has  collected  and  analysed 
115  cases  of  gangrene  associated  with  enteric  fever,  and  due  to  plugging  of 
the  ari;eries.  In  twenty-one  cases  arterial  thrombosis  was  observed  without 
gangrene,  the  absence  of  which  is  much  more  common  with  thrombosis  of 
arteries  of  the  upper  extremity  than  of  tlie  lower.  The  earliest  appearance 
of  the  gangrene  was  on  the  fourteenth  day;  the  latest  in  the  seventh  week. 
In  the  great  majority  of  cases  the  thrombus  was  seated  in  the  arteries  of 
the  extremities;  and  in  those  of  the  lower  far  more  frequently  than  of  the 
upper.  In  eight  out  of  eleven  cases  of  arterial  thrombosis  of  the  lower 
extremities,  collected  by  Barie,  the  posterior  tibial  artery  was  concerned.  In 
contrast  with  venous  thrombosis  the  right  side  is  the  seat  as  often  as  the  left. 

Other  arteries,  as  the  pulmonar}-,  the  superior  mesenteric,  and  the  cerebral, 
may  become  thrombosed.  Four  fatal  cases  of  typhoidal  thrombosis  of  tlie 
middle  cerebral  artery,  or  its  branches,  have  been  reported  (Huguenin, 
Barberet  and  Chouet,  Vulpian  and  Osier) ;  and  other  cases  have  been 
recorded  in  which  the  diagnosis  of  cerebral  thrombosis  was  made  from  the 
symptoms.  In  Osier's  case,  in  which  Dr.  Flexner  and  I  examined  the  brain, 
the  middle  cerebral  artery  was  open ;  but  the  ascending  parietal  and  parieto- 
temporal arteries  and  their  branches  were  occluded  by  adherent,  firm,  mixed 
thrombi.  The  adjacent  brain  substance  was  studded  with  punctiform 
haemorrhages,  but  not  much  softened.  Typhoid  bacilli  were  \Wdely  distrib- 
uted in  the  body. 

The  arterial  thrombosis  may  be  secondary  to  embolism;  but  in  the  great 
majority  of  cases  it  has  been  reported  as  autochthonous.  In  the  older 
records  the  thrombosis  has  been  usually  regarded  as  marantic ;  whereas  the 
tendency  now  is  to  refer  it  to  an  infective  arteritis;  a  view  which  is  prob- 
able, although  we  have  few  conclusive  observations  in  its  support.  Eattone 
and  Haushalter  claim  to  have  demonstrated  the  typhoid  bacillus  in  the  walls 
of  occluded  arteries ;  and  Gilbert  and  Lion,  Crocq,  and  Boinet  and  Eamary 
have  produced  an  acute  aortitis  experimentally,  by  injuring  the  vessel  wall 
and  then  injecting  typhoid  bacilli  into  the  circulation.  The  bacteriological 
studies  are  too  meagre  and  unsatisfactory  to  warrant  any  definite  statements 
as  to  the  specific  cause  of  arterial  thrombosis  in  enteric  fever. 

The  far  commoner  venous  thrombosis  of  enteric  fever  has  been  adequately 
considered  by  Professor  Dreschfeld  in  Allbutt's  Syst.  Med.,  vol.  i.  p.  817; 
and  the  points  bearing  on  its  causation  have  been  presented  under  Etiolog}'. 
Richardson  has  called  special  attention  to  the  "  marantic  "  thromboses  of 
intracranial  veins  complicating  enteric  fever. 

Influenza. — Nearly  all  of  our  knowledge  of  thrombosis  in  influenza  dates 
from  the  pandemic  of  1889-90,  wliich  led  to  the  recognition  of  countless 
complications,  among  which  those  of  the  circulatory  system  occupy  a  less 


THROMBOSIS  151 

prominent  place  than  the  respiratory  and  nervous.  Arterial  thrombosis, 
although  far  from  common,  is  still  not  an  extra-ordinarily  rare  complication 
or  sequel  of  influenza.  It  is  more  common  in  this  disease  than  in  any  other 
acute  infection.  In  a  few  instances  it  appeared  as  early  as  the  third  to  the 
fifth  day,  but  in  most  during  convalescence.  Over  forty  cases  of  arterial 
thrombosis  or  of  gangrene  accompanying  or  following  influenza  have  been 
reported.  References  to  many  of  these  will  be  found  in  the  monographs  of 
Leichtenstern  and  of  Lasker;  but  their  lists  are  far  from  complete.  In  a 
partial  collection  of  the  cases  I  find  that  the  popliteal  artery  was  occluded  in 
six ;  the  femoral  in  four ;  the  iliacs,  the  axillary,  the  brachial,  the  pulmonary, 
and  tlie  renal  each  in  two ;  and  the  central  artery  of  the  retina  (embolism  be- 
ing probably  excluded)  in  one.  The  cerebral  arteries  were  repeatedly  invaded. 
In  several  instances  there  were  multiple  thrombi.  Symmetrical  gangrene 
following  bilateral  plugging  was  observed  in  a  number  of  cases.  Gangrene 
was  observed  in  all  the  cases  of  occlusion  of  the  arteries  of  the  lower  extremi- 
ties, but  not  regularly  with  that  of  the  upper. 

It  is  difficult  to  say  in  how  many  cases  the  occlusion  was  due  to  embolism. 
Endocarditis  is  a  rare  but  recognised  complication  of  influenza,  and  globu- 
lar cardiac  thrombi  have  also  been  observed.  In  the  great  majority  of  cases 
it  seems  clear  that  there  was  primary  arterial  thrombosis. 

Venous  thrombosis  is  a  far  commoner  result  of  influenza;  and  has  been 
the  subject  of  a  special  memoir  by  Chaudet,  and  of  numerous  articles  in 
the  medical  journals  of  all  countries.  Twenty-five  cases  are  recorded  in 
Guttmann  and  Leyden's  collective  investigation,  and  many  additional  ones 
are  to  be  found  in  the  vast  literature  on  influenza.  Dr.  Goodhart,  in  his 
article  on  "  Influenza  "  (Allbutt^s  Syst.  Med.,  vol.  i.  p.  683),  notes  the  fre- 
quency and  the  occasional  diagnostic  value  of  this  complication,  which  may 
appear  during  the  course  of  the  disease  or  weeks  afterwards,  and  in  mild  as 
well  as  severe  cases.  In  the  great  majority  of  instances  the  femoral  vein 
was  attacked;  but  the  veins  of  the  upper  extremity  were  thrombosed  more 
frequently  than  in  other  acute  infective  diseases.  Leichtenstern  notes  the 
acute  onset  and  course  in  some  of  the  cases.  There  are  records  of  throm- 
bosis of  the  cerebral  sinuses  in  influenza.  Klebs  and  Kuskow  describe 
capillary  thrombi  in  the  lungs. 

Few  observers  are  satisfied  with  the  explanation  of  either  the  arterial  or 
the  venous  thromboses  of  influenza  as  marantic.  Leyden  suggests  as  a  cause 
increase  of  blood-platelets  from  disintegration  of  leucocytes.  Evidences  of 
such  disintegration,  or  of  masses  of  platelets  in  the  blood,  have  been  noted 
by  Klebs,  Chiari,  and  Baumler.  ]\laragliano  observed  the  onset  of  necro- 
biotic  changes  of  the  red  corpuscles  in  influenza  almost  immediately  after 
withdrawal  of  the  blood.     French  writers  for  the  most  part  attribute  the 


152  THROMBOSIS 

thrombosis  to  infective  arteritis  or  phlebitis  (arterite  grippale,  phlebite 
grippale).  Rendu,  however,  in  his  case  of  arterial  thrombosis  rejects  this 
explanation ;  as  he  found  the  walls  of  the  thrombosed  arteries  entirely  nor- 
mal (nothing  is  said  of  a  microscopical  examination),  and  he  attributes  the 
thrombosis  to  feeble  circulation.  In  his  case  there  was  also  a  thrombus  with 
softened  centre  in  the  left  ventricle,  and  the  occlusion  of  the  artery  may 
have  been  due  primarily  to  an  emlx)lus.  Gerhardt  attributes  tlie  gangrene 
in  his  case  to  spasm  of  the  arteries,  considering  it  therefore  analogous  to 
symmetrical  or  arterio-spastic  gangrene.  In  support  of  the  more  probable 
view  that  the  thrombosis  is  the  result  of  some  change  in  the  vascular  wall, 
directly  referable  to  infection  or  intoxication,  Kuskow  observed  with  great 
frequency  degeneration,  proliferation,  and  desquamation  of  the  vascular 
endothelium  in  influenza.  In  a  fatal  case  of  influenzal  phlegmasia  alba 
dolens  Laveran  found  streptococci  in  the  blood.  These  organisms  have  often 
been  found  in  the  blood  and  organs  of  those  dead  of  influenza. 

In  a  remarkable  case  of  multiple  thrombotic  vegetations  present  in  large 
numbers  in  the  pulmonary  artery,  especially  in  the  left  main  branch,  and  also 
on  the  pulmonary  valves  (other  valves  normal),  Plexner  in  my  laboratory 
foimd  in  the  thrombus,  chiefly  enclosed  within  polynuclear  leucocytes,  very 
numerous,  extremely  delicate  bacilli,  which  were  identified  as  the  influenzal 
bacilli  of  Pfeiffer.  This  establishes  the  occurrence  of  an  acute  arteritis  and 
thrombosis  due  to  the  bacillus  of  influenza. 

Pneumonia. — The  sixteenth  century  error  of  mistaking  for  ante-mortem 
coagula  the  firm,  yellowish  white  cardiac  clots,  intimately  intertwined  with 
the  columnae  carneae,  and  found  after  death  from  pneumonia  more  frequently 
than  from  any  other  disease,  has  not  wholly  disappeared  at  the  end  of  the 
nineteenth  century;  for  coagulation  of  blood  in  the  right  heart  is  still  occa- 
sionally spoken  of  as  a  special  danger  in  pneumonia.  Genuine  ante-mortem 
thrombi  in  the  cavities  of  the  heart  occur  in  pneumonia,  but  they  are  rare; 
being  much  less  common  than  in  many  diseases  in  which  death  from  "  heart- 
clot  "  is  not  mentioned  as  a  special  danger.  Acute  valvular  endocarditis  is 
a  well-recognised  complication  of  pneumonia.  Mention  has  already  been 
made  of  coagula  in  pulmonary  vessels  directly  connected  with  the  inflamed 
lung  (p.  115). 

Benedikt,  Brunon,  Rendu,  Ix'yden,  and  Blagden  have  observed  gangrene 
of  the  extremities  consecutive  to  arterial  thrombosis  in  pneumonia.  Blag- 
den's  patient  was  a  woman  02  yoars  old.  In  Leyden's  case  there  was  throm- 
bosis of  the  lower  end  of  the  abdominal  aorta.  Gangrene  of  the  extremities 
in  pneumonia  may  also  be  the  result  of  embolism;  of  this  event  Osier  has 
observed  an  instance. 


THROMBOSIS  153 

Venous  thrombosis,  although  more  frequent  than  arterial,  is  scarcely 
mentioned  in  text-books  as  a  complication  or  sequel  of  pneumonia.  Few 
cases  have  been  reported.  Da  Costa,  in  a  valuable  article  on  the  subject, 
reports  three  personal  observations,  and  has  collected  from  the  literature 
six  additional  ones,  and  two  which  are  doubtful.  In  addition  to  these,  I 
have  found  reports  of  cases  by  Barbanceys  (two  cases),  Lepine,  Fabrics, 
Valette,  JMya  (tw^o  cases),  and  Lee  Dickinson  (seven  cases),  making  a  total 
of  twenty-three  cases  of  venous  thrombosis  in  pneumonia.  The  femoral  or 
internal  saphenous  veins  were  those  invaded,  the  affection  being  oftener  on 
the  left  than  on  the  right  side.  There  were  at  least  three  deaths  from  pul- 
monary embolism  consecutive  to  the  tlirombosis.  The  affection,  if  one  may 
draw  any  conclusion  from  so  small  a  number  of  cases,  is  more  common  in 
women  than  in  men.  Of  367  cases  of  pneumonia,  observed  by  Dickinson, 
peripheral  venous  thrombosis  occurred  in  seven,  of  which  four  were  in  young 
women,  two  of  these  being  chlorotic.  In  several  instances  of  influenzal 
thrombosis  pneumonia  had  occurred.  I..aache  ranks  pneumonia  next  to 
influenza  and  enteric  fever  as  regards  the  frequency  of  occurrence  of  peri- 
pheral thrombosis;  but  this  event  is  far  commoner  in  the  last  two  diseases. 
The  affection  occurs  during  convalescence,  rather  than  in  the  course  of 
pneumonia ;  and  presents  the  same  general  characters  as  the  phlegmasa  alba 
dolens  of  enteric  fever.  Da  Costa  very  plausibly  attributes  it  to  a  primary 
infective  phlebitis.  Mya,  in  one  of  his  cases,  found  pneumococci  in  large 
numl>ers  in  the  thrombus. 

Acute  Articular  Rheu-matism. — There  was  a  time  when  rheumatic  phle- 
bitis ranked  in  importance  next  to  the  puerperal  form ;  but  it  is  now  recog- 
nised that  most  of  the  cases  of  thrombosis  attributed  by  the  older  writers 
to  rheumatism  had  nothing  to  do  with  acute  articular  rheumatism.  Schmitt 
and  Vaquez  have  sifted  the  reported  cases,  and  they  find  that,  while  phlebitis 
or  venous  thrombosis  is  to  be  recognised  as  a  complication  of  genuine  acute 
rheumatism,  it  is  a  rare  one.  The  infrequeney  of  this  event  is  noteworthy 
in  view  of  the  fibrinous  state  of  the  blood  and  the  frequency  of  acute  endo- 
carditis. Gatay  has  reported  a  doubtful  case  with  negative  result  of  the 
bacteriological  examination  of  the  thrombus.  Legroux  reports  an  instance 
of  thrombosis  of  the  brachial  artery  without  gangrene  in  acute  articular 
rheumatism. 

Appendicitis. — Mention  may  l)e  made  of  the  occurrence  of  thrombosis 
with  appendicitis,  as  this  affection  is  of  medical  as  well  as  surgical  interest. 
Besides  the  septic  thrombo-phlebitis  of  the  mesenteric  and  portal  veins, 
thrombosis  of  the  iliac  and  femoral  veins  may  occur  on  the  left  side  as  well 
as  on  the  right.  The  published  reports  indicate  that  this  is  more  common 
on  the  right  side;  but  in  the  131  cases  of  appendicitis  in  the  service  of  my 
13 


154  THEOMBOSIS 

colleague  Professor  Halsted,  with  the  notes  of  which  Dr.  Bloodgood  has 
furnished  me,  there  were  four  instances  of  peripheral  venous  thrombosis,  all 
of  the  left  leg ;  one  being  limited  to  the  calf.  Three  of  these  were  in  chronic 
appendicitis,  the  operation  being  between  the  attacks.  Mynter,  who  has  also 
observed  thrombosis  of  the  left  femoral  vein,  attributes  it  to  great  prostra- 
tion and  weak  circulation.  It  is  interesting  to  note  the  analogy  of  appen- 
dicitic  thromboses  to  puerperal  thromboses,  where  we  also  have  septic  and 
suppurative  tlirombi  in  veins  inuuediately  adjacent  to  the  inflamed  organ, 
and  less  manifestly  infective  thrombi  in  the  veins  of  the  lower  extremities. 
It  is  probable,  however,  that  the  latter  thrombi  in  appendicitis,  as  well  as 
in  the  puerperal  cases,  are  frequently  caused  by  bacteria,  and  oftenest  by 
streptococci,  which  are  concerned  in  both  affections  with  great  frequency. 
In  one  of  Mynter's  cases  sudden  death  was  probably  due  to  pulmonary  embol- 
ism following  thrombosis  of  the  femoral  vein. 

Other  Acute  Infective  Diseases. — It  would  lead  too  far  to  continue  a 
detailed  inquiry  into  the  association  of  thrombosis  with  other  acute  infective 
diseases.  It  must  suffice  to  specify  typhus  fever,  relapsing  fever,  dysentery, 
erysipelas,  suppurative  tonsillitis,  diphtheria,  variola,  scarlatina,  measles, 
Asiatic  cholera.  In  many  instances  thrombosis,  as  associated  vrith  specific 
infective  diseases,  has  been  due  to  a  secondary  septicemia,  streptococci  being 
the  commonest  secondary  invaders.  The  disposition  in  or  after  typhus  fever 
to  arterial  as  well  as  to  venous  thrombosis  should  be  especially  emphasised. 
Thrombosis  has  been  added  to  the  growing  list  of  complications  of  gonor- 
rhea (Martel,  Perrin,  and  Monteux  and  Lop). 

Tuberculosis. — The  consideration  of  thrombosis  directly  referable  to 
tuberculous  processes  adjacent  to  vessels  need  not  detain  us.  The  occur- 
rence of  intimal  tubercles,  where  the  evidence  is  conclusive  that  tubercle 
bacilli  have  penetrated  the  inner  lining  of  vessels  directly  from  the  circula- 
tion in  the  main  channel,  may  be  mentioned  not  only  as  a  cause  of  throm- 
bosis, but  also  as  an  interesting  illustration  of  this  mode  of  infection  of  the 
vascular  wall.  Several  instances  of  endocarditis  caused  by  the  tubercle 
bacillus  have  been  described,  and  mention  has  already  been  made  of  tubercu- 
lous cardiac  thrombi  (p.  142).  Michaelis  and  Blum  have  produced  vegeta- 
tive tuberculous  endocarditis  experimentally,  by  injuring  the  valves  in  rab- 
bits and  then  injecting  tul)ercle  bacilli  into  the  ear  veins.  Particularly 
demonstrative  of  infection  taking  place  through  the  vascular  enothelium 
are  the  rare  instances  of  tuberculous  foci  in  the  aortic  intima,  without  inva- 
sion of  the  outer  coats,  and  without  tuberculosis  of  neighbouring  parts. 
Two  instances  of  this  form  of  aortic  tuberculosis  have  been  observed  in  my 
laboratory,  and  described  by  Flexner  and  Blumer.  I  have  recently  examined 
a  section,  in  the  possession  of  Dr.  (Jaylord,  of  a  superficial  tuberculous  focus 


THROMBOSIS  155 

in  the  intima  of  the  aorta  with  an  exquisite  platelet  and  fibrinous  thrombus 
containing  tubercle  bacilli  attached  to  the  nodule.  A  similar  case  has  been 
described  by  Stroebe.  These  rare  instances  are  cited  because  they  furnish 
conclusive  proof  that  bacteria  may  penetrate  the  inner  lining  of  vessels  from 
the  main  channel,  even  where  the  blood-current  is  forcible;  and  may  set 
up  inflammation  of  the  intima  with  secondary  thrombosis.  Hektoen's  inter- 
esting observations  of  changes  in  the  intima  of  vessels  in  tuberculous  men- 
ingitis furnish  additional  evidence  along  the  same  lines. 

Arterial  thrombosis,  outside  of  the  forms  to  which  reference  has  just 
been  made,  and  which  are  of  pathological  rather  than  clinical  interest,  is  a 
rare  event  in  tuberculosis.  Most  common  are  the  instances  of  thrombosis 
of  the  pulmonary  artery  or  its  main  branches  in  phthisis.  Dodwell  mentions 
an  instance  of  thrombosis  of  both  popliteal  artery  and  vein.  Vaquez,  in 
chronic  pulmonary  tuberculosis,  describes  an  interesting  case  of  thrombosis 
of  the  left  subclavian,  axillary  and  brachial  arteries  with  gangrene  of  the 
arm :  he  found  streptococci  in  the  plug  and  in  the  wall  of  the  vessel,  includ- 
ing the  vasa  vasorum,  but  no  tubercle  bacilli. 

On  the  other  hand,  peripheral  venous  thrombosis  in  advanced  phthisis  is  a 
comparatively  common  and  well-recognised  ailment.  In  the  great  majority 
of  cases  veins  of  the  lower  extremities,  the  left  oftener  than  the  right,  have 
been  plugged ;  but  the  thrombus  may  be  in  the  inferior  vena  cava,  or  other 
veins,  or  the  cerebral  sinuses.  Dodwell,  in  his  valuable  paper  on  this  sub- 
ject, places  tlie  proportion  of  cases  of  phthisis  with  this  complication  at 
about  3  per  cent.  In  about  1300  necropsies  of  phthisical  patients  at  the 
Brompton  Hospital  there  were  twenty  cases  of  thrombosis  of  veins  of  the 
lower  extremities  (1.5  per  cent). 

The  peripheral  venous  thromboses  of  advanced  phthisis  are  usually  cited 
as  typical  examples  of  tlie  marantic  or  cachectic  form.  Dodwell,  however, 
while  recognising  enfeebled  circulation  as  a  factor,  is  inclined  to  refer  the 
thrombosis  to  some  unknown  change  in  the  vascular  wall  set  up  by  a  compli- 
cating septicaemia.  He  emphasises  the  infrequency  of  venous  thrombosis 
with  the  acute  and  the  very  chronic  forms  of  phthisis,  and  its  relative  fre- 
quency with  an  intermediate  type  with  remittent  or  continued  fever.  He 
also  noted  association  with  intestinal  and  larjTigeal  ulceration  in  a  larger 
percentage  of  the  thrombotic  cases  than  the  average.  As  is  well  known, 
secondary  septicaemias,  usually  streptococcal,  are  very  common  in  phthisis. 

There  are  several  records  of  bacteriological  examination  of  the  peripheral 
thrombi  in  phthisis,  which  show  that  they  may  be  of  mycotic  origin.  Vaquez 
found  tubercle  bacilli,  without  other  micro-organisms,  in  a  thrombus  of  the 
left  profunda  and  femoral  veins.  They  were  present  also  in  the  w^1ll  im- 
mediately beneath  the  endothelium,  but  were  absent  from  the  media  and 


156  THROMBOSIS 

adventitia.  Sabrazes  and  Mongour  in  two  instances  found  tubercle  bacilli 
both  in  the  plug  and  in  the  wall  of  a  thrombosed  iliac  vein :  tliey  were 
associated  with  micrococci.  More  frequently  micrococci,  presumably  py- 
ogeuetic,  have  been  found,  without  tubercle  bacilli,  in  the  thrombi  and 
vascular  walls:  examples  of  this  are  recorded  by  Vaquez.  Notwithstanding 
these  suggestive  bacteriological  findings  it  would  be  quite  premature  to  con- 
clude that  all  the  peripheral  venous  thromboses  of  phthisis  are  referable  to 
direct  infection  of  the  venous  wall  by  bacteria.  In  a  rather  old  thrombus  of 
the  iliac  and  femoral  veins  in  phthisis  I  failed  to  find  any  micro-organisms, 
either  by  culture  or  by  microscopical  examination. 

Ilirtz  has  called  attention  to  the  occurrence  of  phlebitis  in  the  initial 
stage  of  phthisis.  Some  cases  so  reported  have  appeared  to  be  chlorotic  in 
origin. 

Cachectic  States. — Of  other  marasmic  or  cachectic  states,  in  which  throm- 
bosis is  somewhat  frequent,  may  be  especially  mentioned  those  resulting 
from  cancer,  dysentery,  chronic  diarrhoea,  gastric  dilatation,  prolonged  sup- 
purations especially  of  bone,  anaemia  from  loss  of  blood,  and  sj'philis.  The 
association  of  thrombosis  with  syphilis  has  been  recently  discussed  by  Barbe. 
Phthisis  has  just  been  considered.  It  is  especially  in  the  young  and  the  very 
old  that  these  conditions  are  most  likely  to  produce  thrombosis.  Thromboses 
of  the  cerebral  sinuses,  and  of  the  renal  and  other  veins,  in  marasmic  infants, 
particularly  after  diarrhoea,  are  well  recognised.  Peripheral  venous  throm- 
bosis is  more  often  associated  with  the  waxy  kidney  than  with  other  forms 
of  Bright's  disease.  The  throm])i  occasionally  found  in  the  renal  veins  in 
chronic  diffuse  nephritis  are  probably  due  to  local  causes,  and  not  to  cachexia. 

There  is  a  French  thesis  by  Rigollet  on  thrombosis  in  malaria,  and  Pitres, 
Bitot,  and  liegnier  have  likewise  called  attention  to  the  subject.  It  is 
doubtful  whether  there  is  any  relation  between  malaria  and  thrombosis.  In 
over  2000  cases  of  malaria  observed  in  Professor  Osier's  service  at  the  Johns 
Hopkins  IIos])ital  no  instance  of  thrombosis  was  found.  (Personal  com- 
munication by  Dr.  Thayer.) 

Trousseau  attached  some  diagnostic  significance  to  the  occurrence  of 
thrombosis  in  cancer.  There  have  Ix^en  instances  of  latent  cancer  of  the 
stomach  in  which  })eripheral  venous  thrombosis  was  the  first  symptom  to 
attract  attention,  as  indeed  it  was  in  Trousseau  himself  who  died  of  gastric 
cancer.  (Jouget  has  reported  a  c.use  of  widespread  venous  thrombosis,  of 
eight  months'  duration,  which  wjis  tlio  only  affection  obserbed  during  life. 
At  the  autopsy  a  small  cancer  of  the  stomach  was  found.  Dr.  Osier  has  told 
me  of  a  personal  oltservation  of  verj'  extensive  multiple  tliroml)Osis  associated 
with  cancer  of  the  stomach. 

The  j)rincipal  scats  of  cachectic  thromboses  are  tlie  auricular  appendages, 
between  the  columiue  carnea^  of  the  right  heart,  in  the  veins  of  the  lower 


THROMBOSIS  157 

extremities,  the  cerebral  sinuses,  the  pelvic  veins,  and  the  renal  veins.  Lance- 
reaux  has  strongly  urged  that  this  form  of  tlirombosis  never  occurs  in  the 
arteries.  Doubtless  in  not  a  few  reported  cases  embolism  has  not  been 
satisfactorily  excluded;  but  older  observations  of  Charcot  and  von  Reck- 
linghausen, and  several  recent  ones,  leave  no  doubt  of  the  occurrence  of 
genuine  so-called  marantic  or  cachectic  thrombi  in  arteries,  even  in  the 
aorta. 

While  pre-existing  vascular  disease,  particularly  angio-sclerosis  and  vari- 
cose veins,  are  predisposing  conditions,  these  plugs  are  often  seated  upon 
intimae  which  show  very  slight  alteration.  Indeed  competent  observers  have 
repeatedly  described  the  vessel  wall  beneath  marantic  tlirombi  as  normal. 
While  secondary  septic  infections  often  participate  in  the  causation  of 
cachectic  thromboses,  the  view  that  all  have  this  origin  is  at  present  un- 
substantiated. It  is  clear  that  enfeebled  circulation  is  of  importance  in 
their  causation;  but,  for  reasons  already  stated,  there  must  be  some  addi- 
tional element,  which,  in  many  cases  at  least,  cannot  well  be  other  than 
changes  in  the  composition  of  the  blood.  The  nature  of  these  changes  is 
not  known.  Possibly  increase  of  platelets,  or  a  special  vulnerability  of  cells, 
perhaps  of  the  red  corpuscles  from  which  platelets  are  derived,  may  be 
concerned. 

Cardiac  Incompetency. — I  have  already  had  occasion  in  this  article  to 
speak  repeatedly  of  the  importance  of  feebleness  of  the  general  circulation 
in  the  causation  of  thrombosis.  Thrombi  in  the  heart  itself  have  been  con- 
sidered (p.  139).  In  this  respect  attention  is  called  to  the  occurrence  of 
peripheral  venous  thrombosis  in  chronic  passive  congestion  due  to  cardiac 
incompetency,  chiefly  from  valvular  disease.  Especially  noteworthy,  in  view 
of  the  slow  venous  circulation  and  the  frequency  of  cardiac  thrombi  in  this 
condition,  is  the  infrequency  of  peripheral  thrombosis.  Hanot  and  Kalm, 
in  reporting  an  instance  of  thrombosis  of  the  right  subclavian  vein,  say  that 
they  were  able  to  find  in  the  French  literature,  which  is  exceptionally  rich 
in  clinical  contributions  to  the  subject  of  thrombosis  and  phlebitis,  only  five 
additional  observations  of  peripheral  venous  thrombosis  in  cardiac  disease, 
I  do  not  tliink  that  tliis  complication  is  quite  so  rare  as  would  appear  from 
this  statement;  for,  without  any  systematic  effort  to  collect  cases,  I  have 
found  records  of  eighteen  additional  ones — Ramirez  (two  cases),  Baldwin, 
NicoUe,  HirschlafE  (two  cases),  Robert,  Ormerod,  Mader,  Huchard  (two 
cases),  Cohn  (three  cases),  Cheadle  and  Lees  (three  cases  reported  by  Poyn- 
ton)  ;  and  I  have  observed  two  instances  of  femoral  and  iliac  thrombosis 
associated  with  mitral  regurgitation. 

The  most  notable  fact  concerning  these  twenty-six  cases  is  that  seventeen 
were  thromboses  of  veins  of  the  neck  or  upper  extremity  or  both,  far  more 


158  THROMBOSIS 

frequently  of  the  left  than  the  right  side;  and  one  of  the  innominate  veins. 
In  one  of  Cheadle  and  Lees'  cases  the  innominate,  subclavian,  axillary,  and 
internal  and  external  jugular  veins  upon  both  sides,  the  left  inferior  thyroid, 
and  the  upper  two-thirds  of  the  superior  vena  cava  were  thrombosed;  and 
in  another  of  their  cases  both  internal  jugulars  and  both  innominates  were 
completely  plugged,  and  there  was  a  mural  thrombus  in  the  upper  part  of 
the  superior  vena  cava.  It  may  be  that  femoral  thrombosis  is  more  conmion 
in  heart  disease  than  would  appear  from  these  figures;  it  is  less  likely  to  be 
reported  than  thrombosis  of  the  neck  and  arms,  and,  on  account  of  the 
oedema  attributable  to  cardiac  insufficiency,  may  more  readily  be  overlooked 
both  at  the  bedside  and  the  autopsy  table.  When,  however,  we  consider  that 
Bouchut  places  the  ratio  of  thromboses  of  the  upper  extremity  to  those  of 
the  lower  at  1  to  50,  the  relatively  large  number  of  tlie  former  associated 
with  cardiac  disease  is  certainly  most  striking.  The  clinical  histories  seem 
to  show  that  thrombosis  is  more  likely  to  occur  in  the  cases  witli  tricuspid 
regurgitation  than  in  others;  but  it  is  certainly  even  then  a  verj-  rare  event. 
In  several  cases  there  was  some  complication,  especially  pressure  on  the 
veins  and  tuberculosis.  The  explanation  of  the  greater  frequency  of  the 
thrombosis  on  the  left  than  the  right  side  has  already  been  given  (p.  138). 

The  relative  freedom  from  peripheral  venous  thrombosis  in  cardiac  dis- 
ease, in  spite  of  conditions  of  the  circulation  apparently  favourable  to  such 
an  occurrence,  may  perhaps  be  attributable  partly  to  the  reduction  in  plate- 
lets in  this  condition  (which  has  been  noted  by  van  Emden),  and  partly  to 
the  absence  of  von  Recklinghausen's  "  Wirbelbewegung  "  (p.  138),  an  irregu- 
larity of  the  circulation  which  occurs  especially  in  vessels  too  wide  in  pro- 
portion to  the  amount  of  blood  which  they  receive.  Hanot  and  Kahn  refer 
the  thrombosis  to  a  cachectic  state  developing  in  the  last  stages  of  cardiac 
disease.  Huchard  likewise  attributes  it  to  cardiac  cachexia  associated  with 
secondarj'  infection.  Cheadle  and  Lees'  three  cases  are  referred  by  Poynton, 
who  reports  them,  to  rheumatic  infection.  The  bacteriological  examination 
was  negative. 

As  will  appear  later  (p.  244),  there  is  evidence  that  arterial  plugging 
associated  with  mitral  stenosis  is  due  oftener  to  primary  thromlx)sis  than  is 
generally  supposed. 

Chloroids. — The  association  of  tiironibosis  with  chlorosis  is  of  peculiar 
interest.  Professor  Allbutt,  in  his  article  on  "  Clilorosis  "  ( Allbutt's  "  Sys- 
tem of  Medicine,"  V,  p.  508),  has  sketched  the  more  essential  features,  but 
ha.s  referred  some  p<^>ints  for  consideration  here..  In  the  older  literature  there 
arc  reports  of  plugging  of  the  veins  in  young  women  which  undoubtedly  per 
tain  to  chlorosis.  Thus  William  Sankey,  in  1814,  says:  "  I  have  met  with 
two  cases  in  young  women,  not  after  parturition  ;  both  were  severe  and  weU 


THROMBOSIS  159 

marked;  both  had  obstructed  menses."  But  Trousseau,  with  his  pupil 
Werner,  in  1860  was  the  first  to  draw  distinct  attention  to  tliis  association. 
References  to  the  more  important  records,  up  to  1898,  will  be  found  in  the 
recent  article  by  Schweitzer,  from  Eiclihorst's  clinic. 

Although  tlirombosis  is  not  a  common  complication  of  chlorosis,  it  is 
sufficiently  frequent  to  indicate  a  special  tendency  to  its  occurrence  in  this 
disease ;  a  tendency  calculated  to  arrest  attention  on  account  of  the  age  and 
the  class  of  the  patients,  the  obscure  causation,  and  the  unexpected  and 
calamitous  termination  which  it  may  bring  to  a  disease  ordinarily  involving 
no  danger  to  life.  Some  idea  of  tbe  frequency  of  chlorotic  thrombosis  is 
perhaps  afforded  by  the  statements  that  von  Noorden  observed  5  instances 
in  230  chlorotics,  and  Eiclihorst  4  in  243.  The  list  of  reported  cases  was 
brought  by  Proby  in  1889  to  21,  by  Bourdillon  in  1892  to  32,  and  by  Schweit- 
zer in  1898  to  51.  I  have  found  reports  of  30  additional  cases  not  included 
in  these  lists,  and  am  indebted  to  Dr.  W.  S.  Thayer  for  an  unpublished 
personal  observation;  making  a  total  of  82.  (References  will  be  found  at 
the  end  of  this  article.)  I  have  also  seen  12  other  cases  mentioned,  but  with- 
out sufficient  detail  for  statistical  analysis;  and  I  have  come  across  several 
references  to  articles  on  the  subject  not  accessible  to  me.  Slavic  and  Italian 
literature  has  not  been  searched,  and  the  American  to  only  a  small  extent. 
I  have  no  doubt  that  mention  or  reports  of  over  100  cases  of  thrombosis 
chlorotica  could  be  gathered  by  thorough  overhauling  of  medical  books  and 
periodicals.  Thirty-one  of  my  cases  are  from  French  literature,  twenty-five 
German,  eighteen  English,  three  Scandinavian,  two  American,  and  one 
Italian.  It  would,  however,  be  quite  unwarrantable  from  this  literary  in- 
equality to  infer  any  difference  in  the  incidence  of  the  affection  according  to 
race  or  country. 

The  statistical  study  of  these  eighty-two  cases  brings  out  a  number  of 
interesting  points,  of  which  some  only  are  directly  pertinent  to  this  article. 
Thrombi  in  the  heart  are  very  rarely  mentioned  in  the  post-mortem  reports. 
There  were  only  four  instances  of  primary  arterial  thrombosis,  two  being  of 
the  middle  cerebral  arteries  (Vergely)  ;  one  of  the  pulmonary  (Rendu) 
without  thrombosis  elsewhere,  and  one  of  the  right  axillary  (Tuckwell)  with 
gangrene  of  the  hand  and  recovery.  Dr.  Tuckwell  reports  his  case  as  one  of 
embolism ;  but  it  is  usually  included  among  the  arterial  thromlx)ses,  and 
probably  with  as  much  or  as  little  right  as  the  others. 

All  the  remaining  78  cases  were  venous  thromboses.  There  was  throm- 
bosis of  the  cerebral  sinuses  in  32  cases  (39  per  cent),  6  (19  per  cent)  of 
these  being  associated  with  thrombosis  of  the  lower  extremities.  In  four 
instances  thrombi  extended  from  the  sinuses  into  the  internal  jugular  veins. 
Unquestionably   sinus-thrombosis   is   represented   by   too   high   percentage 


160  THROMBOSIS 

figures  in  my  list,  for  the  obvious  reason  that  reports  of  an  affection  of  such 
gravity  and  such  interest,  especially  to  neurologists,  are  much  more  likely 
to  get  into  print  tiian  those  of  ordinary  femoral  tlirombosis.  Still  the  figures 
are  impressive,  and  indicate  that  sinus-thromhosis  is  not  of  great  rarity  in 
chlorosis;  to  which  malady  a  leading  place  among  the  causes  of  spontaneous 
thrombosis  of  the  cerebral  veins  and  sinuses  in  women  must  be  conceded. 

In  51  of  the  82  cases  there  was  venous  thrombosis  of  the  extremities 
(62.2  per  cent — too  low  a  percentage  as  already  explained)  ;  50  being  of  the 
lower  and  three  of  the  upper,  of  which  only  one  was  limited  to  the  upper 
extremity.  Of  the  50  cases  of  throm])Osis  of  the  lower  extremities  (which 
are  probably  involved  in  at  least  80  per  cent  of  all  chlorotic  thromboses), 
the  process  was  bilateral  in  46  per  cent,  and  unilateral  in  54  per  cent — 
34  per  cent  being  left-sided  and  20  per  cent  right-sided.  The  usual  prefer- 
ence of  femoral  thrombosis  for  the  left  side  is  shown  by  the  l>eginning  of  the 
affection  in  the  left  leg  in  64  per  cent  of  tlie  thromlwses  of  the  lower  ex- 
tremities, in  the  right  leg  in  29  per  cent,  and  on  both  sides  simultaneously 
in  7  per  cent.  There  is  in  the  list  one  case  (Kockel's)  with  meagre  histor}', 
in  which  no  mention  is  made  of  thrombi  outside  of  tlie  upper  part  of  the 
inferior  vena  cava;  death  ensued  from  pulmonary  embolism.  This  I  have 
not  included  among  the  thromboses  of  the  extremities. 

So  large  a  proportion  of  thromboses  involving  both  lower  extremities 
merits  emphasis  as  a  characteristic  of  chlorotic  thrombosis.  So  again  the 
repeated  observations  of  multiple  and  successive  thromboses,  relapses  and 
recurrent  attacks  (it  may  be  after  weeks  or  after  years),  all  point  to  the 
peculiar  and  widespread  tendency  of  thrombosis  in  some  cases  of  chlorosis. 
The  most  remarkable  example  of  tliis  is  Iluels'  case,  in  which  various  large 
veins  of  the  extremities,  trunk  and  neck  became  thrombosed  in  quick  succes- 
sion, until  finally  only  the  jugular  and  right  subclavian  veins  remained  free. 
The  patient  recovered.  In  five  cases  examined  after  death  the  inferior  vena 
cava  was  plugged ;  and  in  a  few  of  those  who  recovered  the  symptoms  indi- 
cated extension  of  the  thrombus  from  the  iliacs  into  this  vein. 

Wliile  tlie  prognosis  of  chlorotic  sinus-thrombosis  is  extremely  bad,  Bris- 
towe  and  Buzzard  each  report  an  instance  of  recovery.  Such  a  possibility 
has  been  questioned,  but  I  see  no  reason  to  doubt  it.  Not  very  infrequently 
after  death  in  one  or  more  of  the  intracranial  sinuses  thrombi  are  found  wliich 
had  occasioned  no  recognisable  symptoms  during  life,  and  no  lesions  of  the 
brain. 

A  fatal  issue  of  uncomplicated  thrombosis  of  the  extremities  is  due  almost 
always  to  pulmonary  emlwlism,  which  occurs  oftenest  in  the  second  to  the 
fourth  week  after  the  onset,  and  usually  after  some  movement  of  the  body. 
In  my  collection  of  ca-ses  there  are  tiiirtcen  instances  of  pulmonary  embolism 


THROMBOSIS  161 

(25  per  cent  of  the  fifty-two  cases  with  venous  thrombosis  outside  of  the 
cerebral  sinuses) .  All  but  two  terminated  fatally.  In  some  other  cases  there 
were  symptoms  suggestive  of  embolism;  and  doubtless  emboli  lodged  in 
smaller  pulmonary  arteries  without  giving  any  indication  of  their  presence. 
After  making  due  allowance  for  the  undoubtedly  disproportionate  repre- 
sentation of  embolism  of  the  large  pulmonary  arteries  in  published  records, 
this  catastrophe  remains  sufficiently  frequent  to  impart  a  certain  gravity  to 
the  prognosis  even  of  simple  femoral  tJirombosis  in  chlorosis. 

There  are  almost  as  many  hypotheses  of  chlorotic  thrombosis  as  of 
chlorosis  itself.  None  of  these  introduces  any  factors  which  have  not  been 
considered  already  under  etiology.  The  principal  causes  which  have  been 
assigned,  either  singly  or  in  combination,  may  be  grouped  as  follows:  (i.) 
feeble  circulation  due  to  weakness  of  the  heart,  sometimes  intensified  by 
congenital  hypoplasia  of  the  blood-vessels  (Virchow)  ;  (ii.)  alteration  of 
the  vascular  endothelium,  especially  fatty  degeneration  (Eichhorst,  Renaut)  ; 
(iii.)  primary  phlebitis  of  unknown  causation  (Vaquez)  ;  (iv.)  increase  of 
platelets  (Hanot  and  Mathieu,  Buttersack) ;  (v.)  some  fault  in  the  com- 
position of  the  blood,  variously  defined  as  lowered  specific  gravity,  deficiency 
of  salts  (  ?)  (Renaut),  presence  of  extractives  derived  from  muscular  activity 
(Proby),  increase  of  fibrin-ferment  (Birch-Hirschfeld)  ;  (vi.)  secondary 
infection  (Villard,  Rendu,  Oettinger,  von  Noorden). 

It  is  not  necessary  here  to  discuss  all  these  views  in  detail.  The  data  for 
estimating  their  value  have  for  the  most  part  already  been  presented  in  this 
article.  Such  primary  lesions  of  the  vascular  wall  as  have  been  noted  in  the 
thrombosed  veins  have  usually  been  trivial,  and  are  common  enough  without 
thrombosis.  There  is  at  present  no  bacteriological  basis  for  the  infective 
supposition.  Villard's  much-quoted  observation  is  unconvincing;  in  his 
case  a  small  piece  of  a  peripheral  thrombosed  vein  was  excised  and  examined 
by  Nepveu  for  micro-organisms  with  negative  result,  Villard  adds  that 
Bossano  found  micro-organisms  in  the  blood,  but  gives  no  details ;  and  there 
is  no  evidence  tliat  these  micro-organisms  may  not  have  come  from  the  skin. 
Perhaps  more  weight  should  be  attached  to  a  few  observations  in  which  some 
source  of  infection,  such  as  furuncle,  was  present.  Proby,  Lowenberg,  von 
Xoorden,  and  other  observers  have  examined  the  thrombi  and  blood  of 
chlorotics  without  finding  any  micro-organisms.  Nevertheless  von  Noorden 
and  others  are  favorably  disposed  to  the  infective  hypothesis,  on  clinical 
grounds.  Sometimes  the  onset  of  chlorotic  thrombosis  is  ushered  in  by  a 
chill  or  chilly  sensations;  usually  there  is  fever,  which  may  be  well  marked; 
and  in  general  the  S}Tnptoms  are  thought  by  some  to  indicate  infection.  It 
does  not  seem  to  me  imperative  to  interpret  these-  symptoms  as  necessarily 
indicative  of  infection  by  micro-organisms. 


162  THROMBOSIS 

There  are  difficulties  with  all  of  the  hypotheses  which  have  been  sug^gested. 
I  think  that  there  may  be  some  significance  for  the  etiology  of  chlorotic 
thrombosis  in  the  increase  of  platelets  noted  by  Hanot  and  Mathieu,  and  by 
Hayem;  and  determined  more  accurately  by  Muir.*  I  shall  also  venture  to 
suggest  that  there  may  be  some  nutritive  disturbance  of  the  red  corpuscles, 
in  consequence  of  which  they  disintegrate  more  readily  from  slight  causes, 
and  produce  the  granular  material,  chiefly  platelets,  which  constitutes  the 
beginning  wliite  thrombus;  and  in  support  of  this  opinion  I  will  call  atten- 
tion to  Maragliano  and  Castellino's  observations  of  the  lowered  resistance  of 
chlorotic  red  corpuscles.  Another  element  which  may  enter  into  the  causa- 
tion is  some  little  understood  irregularity  of  the  circulation,  other  than  re- 
tarded flow,  which  is  manifested  in  the  venous  thrills  and  hums ;  and  which 
may  in  certain  situations,  where  thrombi  most  frequently  form  (sinuses, 
femoral  vein),  lead  to  the  eddies  shown  by  von  Recklinghausen  to  be  of 
importance  in  the  causation  of  thrombosis;  although  I  confess  that  the 
fullness  of  the  veins  in  chlorosis  does  not  support  this  suggestion. 

Gout. — Since  the  publication  of  the  classical  paper  on  gouty  phlebitis  by 
Paget  in  1866,  followed  by  those  of  Prescott  Hewett  and  Tuckwell,  this 
affection  has  been  well  recognised  (see  art.  on  "  Gout,"  Allbutt's  "  System 
of  Medicine,"  IV,  p.  161).  Its  causation  is  unkno^vn,  Paget  with  much 
reason  regards  the  ailment  as  a  primary  phlebitis  with  secondary  thrombosis ; 
and  in  this  he  has  been  followed  by  most  writers  on  the  subject.  Although 
deposition  of  urates  has  been  found  in  the  sheaths  of  veins,  there  is  no  evi- 
dence that  gouty  phlebitis  is  caused  in  this  way.  Sir  W.  Roberts,  on  p.  172 
of  the  article  just  quoted,  ingeniously  suggests  that  the  presence  of  scattered 
crystals  of  sodium  biurate  in  the  blood  may  constitute  foci  around  which 
thrombi  may  be  formed. 

Idiopathic  Thrombosis. — Paget  says  that  the  occurrence  of  phlebitis  in 
elderly  persons  without  any  evident  external  cause  warrants  the  suspicion  of 
gout ;  and  that  this  is  perhaps  the  most  common  form  of  idiopathic  phlebitis. 
There  remain,  however,  rare  instances  of  apparently  spontaneous  thrombo- 
j)hlebitis,  occurring  in  previously  healthy  individuals,  which  cannot  be  ex- 
plained in  this  way.  Daguillon  has  observed  and  collected  a  number  of 
such  cases. 

'  Buttersack  has  recently  described  the  presence  in  the  blood  of  chlorotics  of 
cylindrical  masses  of  platelets  identical  with  the  first  form  of  Litten's  blood- 
cylinders.  These  he  considers  to  be  capillary  platelet-thrombi,  which  have  been 
washed  out  by  the  circulatinR  blood.  While  they  may  occur  in  other  conditions, 
Buttersack  associates  them  especially  with  chlorosis.  It  remains  to  be  determined 
whether  this  cast-like  arrangement  of  platelets  is  not  the  result  of  the  mode  of 
preparation  of  the  specimen  of  blood. 


THROMBOSIS  163 

Primary  Infective  Thrombosis. — There  are  rare  instances  of  arterial  and 
venous  thrombosis,  generally  widespread,  wliich  present  the  characters  oJ 
an  acute  infective  disease  without  anatomical  lesions  other  than  the  thrombo- 
phlebitis, or  thrombo-arteritis,  and  the  changes  consecutive  to  the  vascular 
obstruction  and  to  the  vascular  or  general  infection.  The  thrombosis  may 
be  referable  to  a  primary  infective  angeiitis,  or  to  a  general  infection  wuh 
changes  in  the  blood  and  circulatory  disturbances.  The  former  class  of 
cases  may  be  considered  analogous  to  mycotic  endocarditis,  the  localisation 
being  in  the  vascular  intima  instead  of  in  the  endocardium.  In  the  latter 
group,  which  probably  is  not  strictly  separable  from  tlie  former,  the  veins 
or  the  arteries  are  plugged  with  thrombi,  which  are  often  extensive  and 
multiple.  The  venous  is  more  common  than  the  arterial  form.  Vessels 
both  of  the  extremities  and  of  the  viscera  may  be  invaded.  The  affection 
appears  as  an  acute  infective  fever  with  the  special  localisation  of  the 
process  in  the  blood-vessels. 

As  belonging  to  the  group  of  primar}'  infective  thrombo-phlel)itides  I 
should  interpret  a  case  reported  by  Dowse.  A  woman,  43  years  old,  pre- 
viously in  good  health,  was  suddenly  seized  with  chills,  fever,  and  great 
prostration,  accompanied  by  the  rapid  onset  of  severe  pain  and  oedematoiLS 
swelling  of  the  right  leg.  Death  occurred  after  two  and  a  half  weeks.  At 
the  autopsy  the  iliac,  femoral,  popliteal,  and  deeper  veins  were  found  to  be 
filled  with  mixed,  adherent,  predominantly  red  thrombus.  The  tissues 
around  the  thrombosed  vessels  were  suffused  with  blood. 

Osier  has  reported  an  instance  of  the  arterial  form  of  primary  infective 
thrombosis.  A  man,  aged  20,  who  had  recovered  from  tj'phoid  fever  two 
years  previously,  presented  fever,  rapid  pulse,  diarrhoea,  and  abdominal  pain, 
followed  by  gangrene  of  both  legs  extended  to  the  middle  of  the  thighs.  He 
died  about  two  weeks  from  the  beginning  of  the  illness.  At  the  autopsy  was 
found  thrombosis  of  the  femoral  and  iliac  arteries,  of  the  lower  two  inches 
of  the  abdominal  aorta,  and  of  two  large  branches  of  the  splenic  artery.  The 
spleen  was  enlarged,  and  contained  large  infarcts,  one  the  size  of  an  orange, 
which  had  given  rise  to  peritonitis.  There  were  infarcts  also  in  the  right 
kidney.  Numerous  micrococci  were  found  in  the  splenic  infarct,  and  in  the 
exudate  covering  it.  The  heart,  the  intestine,  the  brain,  and  the  lungs 
showed  no  lesions. 

Effects  and  Symptoms. — The  lesions  and  the  symptoms  produced  by 
thrombi  are  referable  to  the  obstruction  of  the  circulation  caused  by  the  plug, 
and  to  the  local  and  constitutional  effects  of  irritative  or  toxic  substances 
which  may  be  present  in  the  thrombus  or  vascular  wall.  It  is  obvious  that 
these  effects  must  vary  with  the  functional  importance  of  the  part  supplied 
by  the  obstructed  vessel ;  with  the  rapidity,  extent,  and  completeness  of  the 


164  THROMBOSIS 

obstruction ;  with  the  location  of  the  plug  in  heart,  artery,  capillary,  or  vein  ; 
with  the  size  of  the  vessel ;  witli  the  readiness  of  establishment  of  a  collateral 
circulation;  with  the  nature  of  the  thrombus,  and  with  associated  local  and 
general  morbid  conditions.  Thus  the  obstruction  of  each  important  vessel 
produces  its  own  anatomical  and  clinical  picture.  The  thromboses  of  certain 
vessels,  as  the  intracranial  sinuses,  the  portal  vein,  the  femoral  vein,  are  well 
characterised,  distinct  affections,  which  receive  separate  consideration  in 
medical  books.  But  I  know  of  no  modern  work  which  presents  in  a  syste- 
matic and  tliorough  way  the  anatomical  and  clinical  characters  of  occlusion 
of  each  of  the  important  vessels  of  the  body;  although  scattered  through 
medical  literature  is  a  large  and  to  a  considerable  extent  unutilised  casuistic 
material  for  such  monographic  treatment.  In  this  article,  treating  of  the 
subject  as  a  whole,  the  more  general  considerations  concerning  the  effects  of 
thrombosis,  with  special  reference  to  certain  common  and  clinically  important 
localisations  which  do  not  receive  separate  treatment  elsewhere  in  this  work, 
will  be  presented.  Widely  different  are  the  effects  according  as  the  throm- 
bosis is  cardiac,  arterial,  capillary,  or  venous. 

Of  Cardiac  Thrombosis. — If  the  presence  of  globular  cardiac  thrombi 
could  be  determined  during  life,  it  would  be  generally  recognized  as  an 
index  of  grave  impairment  of  the  heart's  action.  But,  apart  from  furnish- 
ing emboli,  ordinary  globular  thrombi  are  not  known  to  occasion  any  symp- 
toms. There  may  be  instances  when  during  life  cardiac  thrombi  may  be 
suspected  as  more  probable  sources  of  emboli,  particularly  of  those  causing 
pulmonary  infarction,  rather  than  either  endocardial  vegetations  or  venous 
or  arterial  throml)i ;  but  beyond  conjecture  the  diagnosis  can  hardly  go. 
Gerhardt  attributed  to  the  pressure  of  thrombosed  auricular  appendages 
upon  the  pulmonary  artery  or  aorta  murmurs  heard  over  the  arterial  orifices 
of  the  heart;  but  other  causes  of  such  murmurs  are  commoner  and  better 
recognised.  The  encroachment  of  massive  thrombi  and  of  pedunculated 
polyps  upon  the  orifices  of  the  heart  may  occasion  murmurs,  thrills,  and 
symptoms  indistinguishable  from  those  of  valvular  disease.  In  three  such 
cases,  involving  the  mitral  orifice,  von  Ziemssen  observed  gangrene  of  the 
feet,  which  he  was  inclined  to  refer  to  arterial  thrombosis  rather  than  to 
embolism;  but  this. symptom  has  not  the  diagnostic  value  which  he  assigns 
to  it,  for  in  other  cases  it  was  present  only  exceptionally,  and  it  may  occur 
in  ordinary  mitral  stenosis.  Unless  the  orifices  are  encroached  upon,  the 
mere  presence  even  of  large  thrombi  usually  occasions  little  or  no  distur- 
bance of  the  heart,  or  none  which  can  be  distinguished  from  that  of  asso- 
ciated valvuhxr  or  mural  disease.  The  clinical  features  of  ball-thrombi 
have  already  been  considered   (pp.  145  and  146). 

Of  Arterial  Thrombosis. — The  effects  of  arterial  thrombosis  are  so  much 
like  those  of  embolism  that  it  will  be  convenient  to  defer  the  detailed  con- 


THROMBOSIS  165 

sideration  of  their  manifestations  in  common  to  the  article  on  embolism 
(p.  201),  and  here  to  speak  only  of  the  more  distinctive  features  and  clinical 
types  of  arterial  thrombosis. 

Whether  the  occlusion  of  an  artery  be  by  a  thrombus  or  an  embolus,  the 
result,  apart  from  possibly  infective  properties  of  the  plug,  depends  upon 
the  possibility  of  establishment  of  an  adequate  collateral  circulation.  If 
the  anastomoses  are  such  as  to  permit  the  ready  development  of  a  collateral 
circulation,  an  arterial  branch  may  be  plugged  without  any  mechanical 
effects.  In  the  case  of  certain  visceral  arteries,  as  the  terminal  cerebral, 
branches  of  the  splenic,  and  of  the  renal,  a  collateral  circulation  sufficient 
to  nourish  the  part  supplied  by  the  occluded  artery  cannot  be  established, 
even  with  a  slowly-forming  thrombus.  In  some  situations,  however,  arteries 
whose  abrupt  obstruction  by  an  embolus  may  cause  the  gravest  lesions  and 
symptoms,  may  be  closed  gradually  by  thrombus  without  serious  conse- 
quences. This  has  been  observed  in  thrombosis  of  various  arteries  of  the 
extremities,  neck,  and  trunk;  as  the  femoral,  the  iliac,  the  carotids,  the 
mesenteric,  the  cceliac  axis,  a  main  division  of  the  pulmonary  artery,  and 
even  the  aorta.  But  in  order  to  secure  whatsoever  advantage  may  accrue 
from  its  slower  formation,  the  thrombus  must  find  other  conditions  favour- 
able for  the  development  of  a  collateral  circulation ;  and  often  enough  these 
conditions,  of  which  the  most  important  are  integrity  of  the  arterial  walls 
and  vigour  of  the  general  circulation,  are  absent.  Furthermore,  thrombosis 
is  often  rapid  in  attack,  and  hence,  whether  the  plug  be  a  thrombus  or  an 
embolus,  the  result  is  frequently  the  same. 

In  the  differential  diagnosis  between  arterial  thrombosis  and  embolism 
emphasis  is  properly  laid  in  the  former  upon  the  more  gradual  appearance 
of  the  symptoms  of  vascular  occlusion  and  pre-existing  arterial  disease, 
and  upon  sudden  onset  and  the  detection  of  some  source  for  an  embolus,  par- 
ticularly cardiac  disease,  in  the  latter  (see  "  Diagnosis  of  Embolism,"  p. 
221).  But  mistakes  in  diagnosis  are  sometimes  unavoidable;  for  all  the 
clinical  phenomena  which  attend  the  one  may  occasionally  be  associated  with 
the  other  form  of  arterial  obstruction.  Nor  can  the  distinction  always  be 
made,  with  the  desired  precision,  at  the  autopsy,  although  generally  this 
is  decisive.  Hence  cases  are  reported  as  arterial  thrombosis  which  are  doubt- 
less embolism,  and  conversely. 

Within  recent  years  primary  arterial  thrombosis,  occurring  independently 
of  chronic  diseases  of  the  arteries,  has  been  recognised  as  a  more  frequent 
and  important  affection  than  had  been  generally  supposed  since  the  accep- 
tance of  Virchow's  doctrine  of  embolism.  Of  especial  medical  interest  are 
the  primary  arterial  thromboses,  arising  oftener  as  a  sequel  during  convales- 
cence than  as  an  accompaniment  of  various  infective  diseases,  particularly 


IGG  THROMBOSIS 

of  enteric  fever  and  influenza.  The  associations  and  localisation  of  these 
thromboses,  as  well  as  the  prevailing  view  that  they  are  infective  and  refer- 
able to  an  acute  arteritis,  have  already  been  considered. 

Arterial  Thrombosis  of  the  Extremities. — When,  as  is  usual  arteries  of 
the  lower  extremities  are  affected,  the  first  symptom  is  pain  in  the  limb. 
This  is  often  severe  and  paroxysmal,  and  is  increased  by  pressure  at  certain 
points  in  the  course  of  the  vessel.  The  obliterated  artery  may  be  felt  as  a 
liard,  sensitive,  pulseless  cord;  and  below  it  pulsation  may  be  feeble  or  cease 
altogether.  Before  obliteration  the  pulsations  may  be  of  wider  amplitude 
than  normal,  in  consequence  of  lack  of  arterial  tone  (Gendrin,  Barie).  The 
leg,  especially  about  the  foot  and  ankle,  becomes  pale,  cold,  mottled  with 
blush-red  spots,  numb  and  paretic.  With  loss  of  tactile  sensation  there  is 
often  increased  sensitiveness  to  painful  impressions.  There  may  be  diminu- 
tion or  loss  of  muscular  reaction  to  both  galvanic  and  faradic  currents. 
There  may  be  increased  moisture  of  the  skin,  and  some  oedematous  swell- 
ing of  the  affected  leg.  Unless  adequate  collateral  circulation  be  speedily 
developed  the  termination  is  gangrene.  While  the  extent  of  the  gangrene 
is  in  relation  to  the  seat  of  the  obstruction,  it  varies  also  according  to  the 
collateral  circulation ;  so  that  with  occlusion  of  the  femoral  or  iliacs  it  may 
affect  only  the  foot  or  even  a  toe;  or  with  closure  of  the  popliteal  or  tibial 
arteries  it  may  extend  as  high  as  the  point  of  o])struction.  The  gangrene 
is  usually  dry ;  but  if  septic  inflammation  or  closure  of  the  veins  occurs  it  is 
likely  to  be  moist.  Recovery  may  follow  with  loss  of  the  gangrenous  part; 
or  death  may  result  from  exhaustion,  from  extension  of  the  mortification, 
from  septicaemia  and  toxaemia. 

The  rarer  arterial  thrombosis  of  the  upper  extremities  may  likewise  lead 
to  gangrene ;  but  here  the  chances  for  restoration  of  the  circulation  through 
the  collaterals  are  much  better. 

I  have  already  referred  to  the  relations  of  thrombosis  to  senile,  spon- 
taneous, and  other  forms  of  gangrene  (p.  135).  Hcidenhain  and  Naunyn 
hold  that  arterio-sclerotic  thrombosis  is  the  usual  cause  of  diabetic  gangrene; 
but  further  investigations  into  the  causes  of  this  form  of  gangrene  are 
needed.  Thrombosis  of  the  abdominal  aorta  presents  a  group  of  symptoms 
which  will  be  described  under  Embolism   (p.  243). 

Tlie  complex  of  synij)t<)ms  called  by  Charcot  "  intermittent  claudication  " 
may  be  observed  with  thrombosis  of  arteries  of  the  lower  extremities,  or  of 
the  iliacs  or  abdominal  aorta ;  but  it  is  more  common  with  arterio-sclerosis. 
The  term  "intermittent  claudication*'  (boiterie)  is  used  by  French  vet- 
erinarians to  des<'ribe  similar  symptoms  in  horses  affected  witli  thrombosis  of 
the  iliac  arteries,  which  is  not  a  rare  disease  in  these  animals.  In  these 
cases  the  lower  extremities  receive  enough   blood   for  their  needs  during 


THROMBOSIS  167 

repose,  but  not  during  active  exercise.  The  slighter  manifestations  consist 
only  in  some  muscular  weakness  and  numbness  of  the  legs  after  exercise; 
but  in  more  severe  cases,  after  walking  a  quarter  of  an  hour  or  perhaps  less, 
occur  great  muscular  weakness,  numbness,  and  pains  and  cramps  in  the 
legs,  which  may  become  cold,  exsanguinated,  sometimes  cyanosed  in  the 
peripher}%  and  almost  pulseless.  All  of  these  symptoms  disappear  after 
repose,  perhaps  of  but  a  few  minutes'  duration.  Charcot's  syndrome  has 
in  a  number  of  reported  cases  been  a  precursor  of  arterio-sclerotic  gangrene, 
but  it  may  exist  for  years  without  this  event.  The  phenomena  are  uni- 
lateral or  bilateral,  according  to  the  seat  of  the  arterial  obstruction.  Spasm 
of  the  arteries  is  evidently  an  important  element  in  the  pathogeny  of  inter- 
mittent claudication. 

Other  evidences  of  inadequate  collateral  circulation  with  arterial  throm- 
bosis of  the  extremities  may  be  muscular  atrophy  and  so-called  trophic  dis- 
turbances, which  are  generally  the  result  of  traumatism  or  of  some  infection 
in  tlie  member  whose  natural  resistance  is  lowered  by  the  imperfect  blood- 
supply. 

Thrombosis  of  the  visceral  arteries  may  produce  lesions  and  symptoms 
identical  with  those  following  embolism,  such  as  sudden  death  from  throm- 
bosis of  the  pulmonary  artery,  of  the  coronaries  of  the  heart,  or  of  the 
basilar;  ischsemic  cerebral  softening,  and  infarctions  of  the  lungs,  heart, 
spleen,  kidneys,  retina,  and  intestine,  with  their  attendant  symptoms. 

Thrombosis  of  the  Pulmonary  Artery. — It  is  especially  to  be  noted  that 
thrombosis  of  the  pulmonary  artery,  both  in  its  principal  divisions  and  in 
smaller  branches,  is  often  entirely  latent,  both  as  regards  resulting  lesions  in 
the  lungs  and  the  symptoms.  Thrombosis  of  the  main  trunk  or  primary 
branches  may,  however,  produce  sudden  or  rapid  death;  or  a  sub-acute  or 
chronic  affection  characterised  by  dyspnoea,  cyanosis,  haemoptoic  infarctions 
and  incompetency  of  the  heart,  as  in  a  case  reported  by  Blachez, 

Dr.  Newton  Pitt  believes  that  thrombosis  of  the  pulmonary  arteries  is 
far  more  frequent  than  is  generally  supposed,  even  going  so  far  as  to  say 
"  that  thrombosis  in  the  pulmonary  artery,  so  far  from  being  very  rare, 
possibly  occurs  more  frequently  than  in  any  other  vein  or  SLvtery  in  the  body." 
This  opinion  is  based  partly  upon  failure  to  find  a  source  for  an  embolus; 
in  the  right  heart  or  systemic  veins,  and  partly  upon  absence  of  folding, 
fracture,  or  other  appearances  of  the  plug  suggestive  of  an  embolus,  as  well 
as  upon  association  with  general  conditions  known  to  dispose  to  thrombosis. 
A  similar  remonstrance  against  the  current  interpretation  of  so  many  plugs 
in  the  pulmonary  arteries  as  embolic  in  origin  was  made  by  Bristowe  in  1869. 
In  my  experience  sclerosis  and  fatty  degeneration  of  the  intima  of  the  pul- 
monary vessels  is  not  particularly  uncommon ;  and  I  also  believe  that  pri- 


168  THROMBOSIS 

marv  thrombosis  of  the  pulmonar}'  arteries,  particularly  of  medium-sized 
and  f^maller  branches,  is  more  frequent  than  is  usually  represented  in  text- 
books. Still,  for  reasons  to  be  considered  under  Embolism  (p.  331),  the 
evidence  seems  to  me  in  favour  of  the  usually  accepted  opinion  that  the 
majoritv  of  plugs  found  in  the  pulmonary  artery  and  its  main  divisions  in 
cases  of  sudden  death  are  emboli. 

Thrombosis  of  the  Coronary  Arteries  of  the  Heart."  Cardiac  infarction. — 
Although  the  general  subject  of  infarction  from  arterial  occlusion  is  reserved 
for  the  article  on  embolism,  infarction  of  the  heart  is  caused  so  much  more 
frequently  by  thrombosis  than  by  embolism  that  it  is  more  appropriately 
considered  here. 

Thrombosis  of  the  coronary  arteries  is  in  the  great  majority  of  cases  an 
incident  of  angio-sclerosis  of  the  heart,  an  affection  of  great  clinical  impor- 
tance. It  may  also  result  from  acute  or  chronic  endaortitis  near  the  orifices 
of  these  arteries,  and  possibly  from  acute  inflammation  of  the  coronary 
arteries.  Thrombotic  vegetations,  springing  from  the  aortic  valves,  have 
been  known  to  block  the  mouth  of  one  of  the  coronarj'  arteries. 

There  has  been  much  discussion  concerning  the  existence  of  anastomoses 
of  the  coronary  arteries.  It  has  been  demonstrated  that  anastomoses  exist 
between  the  main  trunks  of  these  arteries,  the  most  important  being  those 
between  the  auriculo-ventricular  branch  of  the  left  coronary  and  branches 
of  the  right  coronary  in  the  sulcus  on  the  posterior  surface  of  the  heart, 
forming  a  horizontal  or  equatorial  auriculo-ventricular  circle  (Haller),  and 
those  between  the  anterior  and  the  posterior  interventricular  branches  near 
the  apex  of  the  heart,  forming  a  vertical  or  meridional  circle.  There  are 
also  anastomoses  on  the  surface  of  the  left  auricle  between  branches  of  the 
left  coronary  and  those  of  the  left  bronchial  artery.  There  are,  however, 
no  anastomoses  between  the  branches  of  the  coronary  arteries  after  they 
have  penetrated  the  myocardium,  these  intramuscular  branches  being  anato- 
mically terminal  arteries. 

These  anastomoses  do  not  usually  suffice  for  the  nutrition  of  the  heart 
after  rapid  occlusion  either  of  the  main  trunks  or  of  intramuscular  branches. 
Throml)osis  of  one  of  the  coronary  arteries  may  be  the  cause  of  sudden  death. 
Barth  reports  the  case  of  a  robust  young  man,  aged  thirty,  who  died  sud- 
denly when  in  apparently  the  best  of  health.  At  the  autopsy  it  was  found 
that  the  moutli  of  the  right  coronary  artery  was  blocked  by  a  thrombus,  tiie 
size  of  a  pea  to  a  l;ean,  attached  to  a  small  atheromatou>i  pate;h  of  the  aorta, 
close  to  the  opening  of  the  right  coronary.    By  a  singular  fatality  this  first 

•  I  regret  not  to  have  noticed  that  this  subject  had  been  presented  by  Sir  R. 
Douglas  Powell  In  Allbutt's  Syst.  Med.,  V,  p.  899.  The  paging  cannot  now  be 
altered. 


THROMBOSIS  169 

and  only  atheromatous  patch  to  be  found  anywhere  in  the  otherwise  per- 
fectly healthy  body  had  formed  at  the  particular  point  where  the  small 
thrombus  springing  from  it  stopped  one  of  the  streams  feeding  the  very 
fountain  of  life. 

Porter  has  shown  experimentally  that  the  frequency  of  arrest  of  the 
heart  after  closure  of  the  coronary  arteries  is  in  proportion  to  the  size  of 
the  artery  occluded ;  and  that  when  arrest  occurs  it  is  preceded  by  a  fall  of 
aortic  pressure  and  an  increase  of  the  diastolic  intraventricular  pressure. 
This  increased  intracardiac  pressure  checks  the  flow  of  blood  in  the  coronary 
veins,  and  thus  interferes  with  the  coronary  circulation  in  the  entire  heart. 

There  are,  however,  many  recorded  cases  which  demonstrate  that  the 
main  trunk  of  one  of  the  two  coronary  arteries  may  be  plugged  by  a  throm- 
bus without  causing  sudden  death.  In  an  instance  reported  by  Dr.  Percy 
Kidd  the  patient  suffered  from  extremely  irregular  and  weak  action  of  the 
heart,  shortness  of  breath,  and  paroxysms  of  dyspnoea;  and  gradually  sank 
from  cardiac  failure.  The  right  coronary  artery,  about  three-quarters  of 
an  inch  from  its  origin,  was  blocked  throughout  by  a  firm,  partly  decolour- 
ised, adherent  thrombus.  The  left  coronary,  particularly  its  descending 
branch,  was  greatly  narrowed  by  sclerosis.  There  were  no  infarctions  or 
fibroid  patches  in  the  heart.  Chiari  has  reported  an  instance  of  thrombotic 
occlusion  of  the  main  stem  of  the  right  coronary  giving  rise  to  an  embolus 
which  lodged  in  the  main  trunk  of  the  left  coronary  artery.  Sudden  death 
was  caused  by  the  latter.  In  areas  supplied  by  the  right  coronary  were 
ischgemic  infarctions  showing  reactive  inflammation.  These,  as  well  as 
the  symptoms  and  the  appearance  of  the  thrombus,  indicated  that  the  main 
trunk  of  the  right  coronary  artery  had  been  closed  for  at  least  several  days 
before  death. 

If  the  patient  lives  long  enough,  the  usual,  but  not  absolutely  imperative, 
anatomical  result  of  thrombosis  either  of  the  main  trunks  or  of  intramuscular 
branches  of  the  coronary  arteries,  is  infarction  in  the  area  supplied  by  the 
occluded  artery.  As  the  descending  or  anterior  interventricular  branch  of 
the  left  coronary  is  by  far  the  most  frequent  seat  of  sclerosis  and  conse- 
quent thrombosis,  the  infarct  is  most  commonly  situated  in  the  lower  part  of 
the  interventricular  septum  and  of  the  anterior  wall  of  the  left  ventricle. 
The  size  of  the  infarct  corresponds  in  general  to  that  of  the  occluded  artery ; 
but,  as  a  rule,  the  infarct  occupies  only  a  part,  sometimes  but  a  small  part, 
of  the  area  previously  supplied  by  the  obstructed  vessel.  Unlike  infarcts 
in  most  other  situations,  those  of  the  heart  are  not,  as  a  rule,  typically 
wedge-shaped,  but  are  often  irregular  in  outline,  and  sometimes  appear  as 
if  several  smaller  areas  of  infarction  had  coalesced;  indeed  there  may  be 
multiple,  detached  infarcts  resulting  from  occlusion  of  a  single  artery. 
14 


170  THROMBOSIS 

Both  pale,  anaemic  infarcts  and  haemorrhagic  infarcts  occur  in  the  heart, 
but  the  former  are  the  more  common.  Fresh,  ana?mic  infarcts  are  swollen, 
firm,  of  an  opaque  yellowish-white  colour,  and  often  present  in  the  margin 
a  zone  of  hypersemia  and  haemorrhage.  Microscopically,  they  are  the  seat 
of  typical  coagulative  necrosis ;  the  muscle  fibres  being  devoid  of  nuclei,  indis- 
tinctly striated  or  homogeneous,  and  of  brittle  consistence.  The  term  myo- 
malacia cordis,  introduced  by  Ziegler,  is  not  a  good  designation  of  the  most 
fresh  infarcts  of  the  heart.  The  infarct  usually  reaches  the  endocardium, 
which  then  presents  a  mural  thrombus ;  and  it  may  extend  to  the  pericardium 
and  cause  a  localised  fibrinous  pericarditis.  A  reactive  inflammation  leading 
to  the  ingrowth  of  granulation  tissue  appears  in  the  margin  of  the  infarct, 
which,  in  course  of  time,  is  absorbed  and  replaced  by  scar  tissue,  unless  it 
become  infected  and  suppurate. 

Cardiac  infarction  may  be  the  cause  of  rupture  of  the  heart,  or  of  a  parietal 
aneurysm ;  or  may  result  simply  in  a  fibroid  patch.  It  is  more  common  than 
would  appear  from  the  meagre  attention  usually  given  to  the  subject  in 
text-books,  and  is  of  much  anatomical  and  clinical  interest. 

The  symptoms  associated  with  coronary  thrombosis  are  those  of  the 
angiosclerotic  heart,  so  that  it  is  hardly  possible  to  make  a  positive  diagnosis 
of  thrombotic  occlusion  of  the  coronary  arteries.  Irregular,  often  slow  pulse, 
shortness  of  breath,  precordial  distress,  angina  pectoris,  sudden  death,  all 
these  may  occur  from  sclerosis  of  the  coronary  arteries,  either  with  or  with- 
out thrombosis.  Fibroid  myocarditis  is  often  present  and  directly  referable 
to  arterial  obstruction ;  but  the  changes  in  the  myocardium  are  probably  of 
much  less  clinical  importance  than  the  underlying  disease  of  the  coronary 
arteries.  R.  Marie  has  recently  published  a  valuable  monograph  on  infarc- 
tion of  the  myocardium  and  its  consequences,  with  a  full  consideration  of 
the  previous  literature  and  the  addition  of  many  new  observations. 

Thrombosis  of  the  mesenteric  arteries  will  be  considered  with  embolism 
of  these  arteries  (p.  237). 

Thrombosis  of  the  cerebral  vessels  will  be  described  in  the  part  of  this 
work  treating  of  diseases  of  the  brain  in  the  next  volume  of  Allbutt's  Syst. 
Med. 

Here  may  lie  mentioned  the  interesting  observations  of  recent  years  con- 
cerning the  dependence  of  certain  diseases  of  the  spinal  cord  upon  affections 
of  the  blood-vessels  of  the  cord,  arterial  thrombosis  being  an  especially 
important  factor  in  many  of  these  cases. 

Capillary  Thrombosis. — In  consequence  of  the  abundant  anastomoses, 
it  is  only  when  all  or  nearly  all  of  the  capillaries  of  a  part  are  thrombosed 
that  any  mechanical  effects  result.  Such  extensive  capillary  thrombosis  is 
more  frequently  the  result  than  tlie  cause  of  necrosis  of  a  part.    According 


THROMBOSIS  171 

to  von  Recklinghausen,  superficial,  often  extensive,  necrosis  of  surfaces,  as 
of  the  skin  and  mucous  membranes,  may  be  caused  by  widespread  hyaline 
thrombosis  of  capillaries  resulting  from  the  energetic  action  of  thermic, 
chemical,  and  even  mechanical  agents.  In  frostbites  and  burns  there  may 
be  extensive  local  hyaline  thrombosis  of  capillaries  and  small  vessels.  I 
have  already  referred  to  my  observations  of  anuria  in  swine,  caused  by  exten- 
sive hyaline  thrombosis  of  the  renal  capillaries  (p.  116).  Although  in 
many  cases  I  have  seen  similar  hyaline  thromboses  in  human  kidneys,  they 
were  never  so  extensive  as  to  seem  likely  -to  cause  recognisable  symptoms. 
Several  years  ago  I  drew  attention  to  tlie  presence  of  hyaline  thromboses 
in  capillaries  and  arterioles  in  the  walls  of  some  fresh  gastric  ulcers,  and 
since  then  I  have  been  able  to  repeat  the  observation  in  three  or  four 
instances. 

Effects  of  Venous  Thrombosis. — Thrombosis  is  so  pre-eminently  an  affec- 
tion of  veins  that  chapters  in  text-books  treating  of  the  general  subject  usually 
pay  scant  attention  to  its  occurrence  in  other  parts  of  the  circulatory  system. 
In  the  veins  thrombosis  occupies  the  field  of  intravascular  plugging  almost 
alone,  for  it  is  only  in  the  portal  system,  and  in  the  rare  instances  of 
retrograde  transport,  that  embolism  enters  into  consideration;  such  extra- 
ordinary occurrences  as  embolism  of  the  azygos  vein,  resulting  from  throm- 
bosis of  the  inferior  vena  cava,  reported  by  Loschner,  being  mere  pathological 
curiosities. 

The  direct  effects  of  venous  thrombosis,  as  of  arterial,  are  referable  to  the 
mechanical  obstacle  to  the  circulation  and  to  the  properties  of  the  throm- 
bus. The  mechanical  effects  result  from  inadequacy  of  the  collateral  circu- 
lation. The  free  venous  anastomoses  in  many  parts  of  the  body  prevent 
any  disturbance  of  the  circulation  as  a  result  of  venous  occlusion  by  simple 
or  benign  thrombi.  Such  innocuous  thromboses  are  particularly  common 
in  the  pelvic  veins.  In  some  situations  veins,  whose  rapid  occlusion  may 
cause  serious  lesions  and  symptoms,  may  be  slowly  plugged  by  a  thrombus 
without  manifest  harm.  For  example,  it  is  not  uncommon  to  find  at  autopsy 
the  main  trunks  of  the  renal  veins  completely  thrombosed,  without  conse- 
quent alteration  of  the  kidney  or  corresponding  symptoms  during  life; 
although  we  know  that  ligation  of  these  veins  causes  haemorrhagic  infarction 
of  the  kidney  with  albuminous,  bloody  urine. 

Frequently,  however,  the  contrast  between  the  effects  of  ligation  and  those 
of  thrombosis  of  veins  is  in  the  other  direction ;  the  thrombosis  being  followed 
by  venous  congestion,  and  the  ligation  of  the  same  veins  being  without  evi- 
dent disturbance  of  the  circulation.  The  latter  difference  is  not  always 
easy  to  explain ;  but  the  factors  to  which  we  can  often  appeal  with  more  or 
less  success,  in  attempting  to  account  for  the  absence  of  sufficient  collateral 


172  THROMBOSIS 

circulation  with  venous  thrombosis,  are  the  extent  of  the  occlusion,  general 
debilit}',  feebleness  of  the  circulation  in  consequence  of  coexistent  anasmia, 
infection,  cachexia  or  constitutional  disorder,  generally  high  venous  pressure 
and  low  arterial  pressure,  lack  of  muscular  movement  and  perhaps  of  other 
subsidiary  forces  aiding  venous  circulation,  phlebosclerosis,  inflammation  or 
some  less  evident  affection  of  blood-vessels  called  upon  for  extra  work,  and 
irritative  or  toxic  properties  of  the  thrombus.  The  importance  of  these,  and 
perhaps  other  accessory  conditions,  in  explaining  the  passive  congestion  of 
many  venous  thromboses  in  human  beings  is  made  evident,  not  only  by  the 
inability  to  produce  similar  effects  experimentally  by  correspondingly  slight 
or  moderate  degrees  of  venous  obstruction,  but  also  by  the  varying  effects 
of  thrombotic  processes  with  the  same  localisation  and  extent  in  different 
persons  and  under  different  conditions.  Thus  femoral  thrombosis  may  be 
attended  by  absolutely  no  oedema  or  passive  congestion,  or  may  occasion 
extreme  degree  of  oedema  and  venous  congestion. 

The  consequence  of  the  passive  hypersemia  caused  by  venous  thrombosis 
is  local  dropsy.  This  constitutes  the  characteristic  symptom  of  uncompen- 
sated venous  obstruction  by  a  thrombus  as  local  necrosis  does  that  of  uncom- 
pensated arterial  thrombosis.  In  addition  to  the  oedema,  there  may  be 
diapedesis  of  red  corpuscles,  but  this  occurs  to  a  perceptible  degree  only  when 
the  obstruction  to  the  venous  flow  is  extreme,  or  the  capillaries  imusually 
permeable.  Such  haemorrhages  are  very  rare  in  peripheral  venous  throm- 
bosis, but  are  common  with  thrombosis  of  the  portal  and  mesenteric  veins, 
the  cerebral  veins  and  sinuses,  the  splenic,  the  retinal,  and  some  other  vis- 
ceral veins.  Actual  necrosis  may  likewise  result  from  thrombosis  of  the 
mesenteric,  cerebral,  and  splenic  veins ;  but,  if  it  occurs  at  all  with  throm- 
bosis of  veins  of  the  extremities,  it  is  extraordinarily  rare,  and  probably  due 
to  complications. 

In  addition  to  these  effects,  due  directly  to  the  blocking  of  the  venous 
circulation,  even  so-called  benign  or  simple  thromboses  often  set  up  an 
acute  inflammation  in  the  venous  wall  and  surrounding  part;  or,  as  already 
explained,  this  inflammation  may  antedate  the  thrombosis.  These  chemical, 
as  distinguished  from  mechanical,  effects  consist  chiefly  in  arterial  hyper- 
apniia,  inflammatory  a?dema,  pain,  implication  of  nerves,  and  constitutional 
symtoms,  such  as  chills,  fever,  and  quickened  pulse.  The  occurrence  of  these 
irritative  or  toxic  effect',  even  with  the  so-called  marantic  thromboses,  is  an 
argument  (in  addition  to  those  already  considered)  in  favour  of  the  infec- 
tive nature  of  many  of  these  plugs,  and  of  their  primarily  phlebitic  origin. 
But  while  undoubtedly  significant  of  such  an  interpretation,  it  can  hardly 
be  considered  conclusive;  for  it  is  possible  that  certain  thrombi  may  possess 
irritative  properties  not  attril)utable  to  the  presence  of  micro-organisms  or 


THROMBOSIS  173 

their  products,  and  that  the  phlebitis,  as  well  as  the  periphlebitis,  may 
be  secondary.  However  this  may  be,  the  old  distinction  between  benign 
and  infective  thrombi  no  longer  appears  so  sharply  marked  as  was  once 
supposed. 

In  rare  instances  the  venous  medical  thromboses  associated  with  anaemic, 
infective,  cachectic,  and  constitutional  diseases  are  plainly  septic,  and  give 
rise  to  phlegmons,  and  perhaps  pyaemia  or  septicaemia.  The  suppurative 
or  septic  thrombophlebitis,  which  with  its  attendant  pyemia  was  in  prae-anti- 
septic  days  such  a  common  and  formidable  wound  complication,  belongs  to 
the  surgeon's  domain,  or,  in  puerperal  sepsis,  to  the  obstetrician's.  (See 
arts.  "  Pygemia  "  and  "  Puerperal  Septic  Disease  "  in  Allbutt's  "  System 
of  Medicine,"  I.)  To  the  borderland  of  medicine  and  surgery  belong  cer- 
tain septic  thrombophlebitides  of  visceral  veins,  of  which  the  most  important 
medical  group,  those  of  the  portal  system,  has  been  considered  by  Professor 
Cheyne  (Allbutfs  "  System  of  Medicine,"  I),  and  by  Dr.  Davidson  in  his 
article  on  "Suppurative  Hepatitis"  (Allbutt's  "System  of  Medicine,"  V, 
p.  123) .  Thrombosis  of  the  umbilical  vessels,  which  may  occur  either  before 
or  after  birth,  may  be  either  simple  or  septic.  The  latter  is  an  important 
affection,  the  consideration  of  which  belongs  to  treatises  on  diseases  of 
infants. 

There  is  perhaps  no  pathological  phenomenon  which,  on  the  face  of  it, 
appears  simpler  of  explanation  than  the  local  oedema  consequent  upon  venous 
obstruction,  but  which,  the  more  it  is  investigated,  turns  out  to  be,  or  at 
least  is  made  to  appear  to  be,  more  complicated.  The  explanation  which 
naturally  occurs  to  one,  and  which  is  often  given,  is  that  the  oedema  is  due 
simply  to  increased  filtration  of  serum  from  the  blood,  in  consequence  of 
the  rise  of  intravenous  and  intracapillary  pressure  resulting  from  the  obstruc- 
tion to  the  venous  circulation.  It  is  certain  that  this  simple  explanation 
does  not  suffice,  at  any  rate  for  most  venous  thromboses,  and  tliat  factors 
other  than  the  mere  rise  of  blood-pressure  in  the  veins  and  capillaries  are 
concerned;  but  as  to  the  nature  of  these  other  factors  there  is  great  differ- 
ence of  opinion.  The  whole  problem  is  vn-apped  up  with  that  of  the  hypo- 
theses of  lymph-formation  and  lymph-absorption,  so  lively  at  the  present  day, 
into  the  discussion  of  which  it  is  impossible  here  to  enter.  Corresponding 
to  the  two  classes  of  these  hypotheses,  we  have  mechanical  hypotheses  and 
vital  or  secretory  hypotheses  of  the  ccdema  of  passive  congestion.  The 
mechanical  explanations  are  at  least  easier  of  comprehension.  Cohnheim 
attributed  this  form  of  oedema  to  increased  venous  and  capillary  pressure, 
combined  with  increased  permeability  of  the  capillary  wall  due  to  malnu- 


174  THEOMBOSIS 

trition."  Starling  and  Cohnstein,  with  full  knowledge  of  the  later  work, 
to  which  they  have  made  important  contributions,  are  advocates  of  a  similar 
explanation. 

Doubtless  several  factors,  although  not  all  necessarily  operative  in  the 
same  case,  are  concerned  in  the  causation  of  the  oedema  of  venous  thrombosis. 
Tiiose  which  seem  to  me  most  apparent  are  the  following:  (i.)  increased 
intro-venous  and  intra-capillary  pressure,  with  consequent  increased  transu- 
dation of  serum  (not  alone  sufficient,  for  tying  the  femoral  vein  or  inferior 
vena  cava  generally  causes  no  oedema)  ;  (ii.)  increased  permeability  of  the 
capillar}'  walls,  which  may  be  due  to  various  causes,  such  as  stretching  from 
larger  content  of  blood,  starvation  and  asphyxia  of  capillary  endothehum 
from  lack  of  fresh  supply  of  nutriment  and  oxygen,  and  injury  from  abnor- 
mal composition  of  blood  in  anaemic,  infective,  cachectic,  and  constitutional 
disease,  or  from  inflammatory  irritants;  (iii.)  diminished  absorption  of 
lymph  in  consequence  of  lack  of  muscular  movement,  of  imbibition  of  the 
capillary  walls  with  fluid,  and  especially  of  retarded  capillary  and  venous 
flow;  (iv.)  arterial  dilatation  from  irritative  or  inflammatory  influences 
emanating  from  adjacent  thrombosed  veins,  probably  also  from  the  asphyxi- 
ated tissues,  and  acting  either  directly  upon  the  arterial  wall,  or  directly 
upon  vaso-motor  nerves,  or  reflexly  (here  the  conditions  resemble  those  in 
lianvier's  well-known  experiment  of  tying  the  inferior  vena  cava  or  femoral 
vein,  and  producing  vaso-motor  paralysis  by  section  of  the  sciatic  nerve)  ; 
(v.)  sometimes  a  watery  condition  of  the  blood  rendering  it  easier  of  filtra- 
tion. Experiments  of  Dr.  Lazarus-Barlow  indicate  that  changes  in  tlie 
chemical  composition  of  the  tissues  and  tissue-fluids  are  also  a  factor  in  the 
production  of  the  oedema."  The  influence  of  hydrostatic  pressure  is  evident 
from  the  greater  frequency  of  oedema  with  thrombosis  of  the  lower  than  of 
the  upper  extremities,  and  from  the  effect  of  position  upon  the  amount  of 
the  oedema.  While  these  various  factors  can  be  conceived  as  essentially  physi- 
cal and  chemical  in  their  action,  tlie  living  capillary  wall  upon  which  they 
act,  either  directly  or  indirectly,  is  to  be  thought  of  as  something  different 
from  a  dead  animal  or  artificial  membrane. 

'"  Cohnheim  is  sometimes  quoted  as  considering  increased  pressure  a  sufficient 
explanation  of  mechanical  oedema,  although  in  his  Allgemeine  Pathologie,  Bd.  I, 
p.  494.  he  expressly  recognises  as  an  additional  factor  "  unknown  Influences  on 
the  part  of  the  living  vessel-wall."  As  I  had  the  opportunity,  when  working  in 
his  laboratory  on  a  problem  concerning  oedema,  to  become  familiar  with  his  views 
on  this  subject,  I  may  be  permitted  to  say  that  he  often  spoke  of  increased  per- 
meability of  the  capillary  wall  as  an  essential  factor  in  the  explanation  of  the 
oedema  of  passive  congestion. 

"  To  these  changes,  as  the  cause  of  alterations  in  osmotic  pressure,  Loeb 
(rniiger's  .\rchiv,  1898,  LXXI,  p.  457)  assigns  the  chief  importance  in  the  pro- 
duction of  oedema. 


THROMBOSIS  175 

Opposed  to  these  mechanical  explanations  are  the  secretory  hypotheses 
of  oedema,  of  which  Hamburger  and  Lazarus-Barlow  are  leading  exponents. 
Of  especial  importance  is  the  work  of  Lazarus-Barlow  upon  the  oedema  of 
passive  congestion.  He  finds  all  the  physical  explanations  inadequate ;  and, 
upon  the  basis  of  interesting  experiments,  he  concludes  that  a  principal 
factor  is  increased  secretion  of  lymph  by  the  capillaries  incited  by  starvation 
of  the  tissues  and  accumulation  of  waste  metabolic  products.  His  "  Manual 
of  General  Pathology  "  may  be  consulted  for  a  full  presentation  of  his  views 
and  a  criticism  of  the  mechanical  hypotheses  of  oedema. 

The  cedema  of  phlegmasia  alba  dolens  is  by  no  means  all  due  to  venous 
congestion,  ^luch,  sometimes  most  of  it,  is  an  inflammatory  oedema  spread- 
ing from  the  thrombosed  veins.  This  is  evident  partly  from  the  hard, 
bra\\aiy,  painful,  at  times  warm  character  of  the  swelling  (oedema  calidiun)  ; 
and  partly  from  its  location  in  the  part  of  the  extremity  nearest  the  affected 
veins.  The  oedematous  swelling  may  begin  above  and  extend  downwards, 
instead  of  in  the  usual  direction  from  below  upwards.  The  hydrarthrosis 
often  associated  in  moderate  degree  with  phlegmasia  is  probably  also  refer- 
able to  an  inflammatory  serous  exudate  rather  than  to  passive  transudation 
from  venous  obstruction.    It  occurs  especially  in  the  knee-joint. 

Thrombosis  of  Veins  of  the  Extremities. — Clinically  the  most  familiar 
form  of  venous  thrombosis  is  that  of  the  extremities;  the  lower  much 
oftener  than  the  upper.  Its  various  sites  and  clinical  associations  have 
already  been  considered  (pp.  136  and  149).  The  affection  may  be  entirely 
latent ;  or  may  be  recognised  by  a  slight  or  moderate  unilateral  oedema  with- 
out general  or  other  local  sjinptoms ;  or  may  be  in  the  form  of  well-marked 
phlegmasia  alba  dolens ;  or  rarely  may  assume  a  severely  infective  character, 
with  chills  and  high  fever;  or,  exceptionally,  may  lead  to  phlegmon  and 
pyaemia  or  septicaemia.  There  is  every  transition  between  the  extremes.  The 
latent  and  milder  t}^es  occur  especially  with  tuberculosis,  cancer,  and  other 
cachexia ;  the  more  severe  manifestations  with  phlebitis  of  the  puerperium, 
infective  diseases,  and  chlorosis ;  but  there  are  many  exceptions  to  this  rule. 

In  the  more  acute  and  well-characterised  cases  the  general  symptoms  are 
chiefly  manifest  at  the  onset;  and  consist  in  moderate  elevation  of  tempera- 
ture, rarely  preceded  by  a  distinct  chill,  oftener  by  chilly  sensations  and 
quickened  pulse.  Increased  frequency  of  the  pulse  may  antedate  the  rise  in 
temperature,  and  the  pulse  may  remain  rapid  after  the  temperature  falls. 
This  disproportion  between  pulse  and  temperature  is  of  diagnostic  value 
(Mahler,  Wyder,  Singer),"^  but  it  is  not  always  present.     These  general 

"Singer  (Arch.  f.  Gynak.,  1898.  LVI,  p.  218)  has  made  a  careful  study  of  the 
pulse-curve  in  puerperal  thrombosis.  A  step-like  acceleration  of  the  pulse-curve 
often  precedes  other  manifestations  of  thrombosis  by  several  days. 


176  THROMBOSIS 

symptoms  of  the  initial  stage,  which  may  persist  for  days,  are  often  over- 
looked; or  they  are  masked  by  an  existing  febrile  disorder.  They  are 
probably  present  in  some  degree,  even  in  mild  eases,  oftener  than  the  clinical 
records  show. 

The  characteristic  symptoms  are  the  local  ones  in  the  affected  leg.  Pain, 
often  paroxysmal,  is  usually  tlie  first  to  attract  attention;  but  sometimes 
it  is  the  cedema.  The  pain  may  be  severe.  It  is  more  or  less  generalised, 
with  especial  tenderness  in  the  groin,  the  inside  of  tlie  tliigh,  the  popliteal 
space,  and  the  calf.  Often  it  is  first  noted  and  may  remain  localised  in  the 
calf ;  as  is  true  of  the  cedema  also.  There  may  be  sensations  of  numbness  or 
of  "  pins  and  needles."  The  cardinal  symptom,  cedema,  sometimes  descend- 
ing sometimes  ascending,  gives  rise  to  the  firm,  painful  swelling  of  the  limb, 
covered  with  tense,  shiny,  smooth,  white  or  mottled  skin,  marked  often  by 
dilated  veins,  whence  comes  the  name  milk-leg  or  white  leg.  The  oedema  in 
typical  phlegmasia  alba  dolens  is  hard  and  elasitc,  pitting  but  little  on  pres- 
sure. Occasionally  the  skin  has  a  more  livid,  cyanotic  hue,  or  it  may  be  of  a 
brighter  red.  In  the  more  acute  cases  the  surface  temperature  is  elevated ; 
in  others  it  is  often  lowered.  Muscular  movements  are  naturally  restrained, 
and  it  is  said  there  may  be  actual  paresis.  The  thrombosed  vein,  if  accessible 
to  palpation,  can  often  be  felt  as  a  hard,  tender  cord;  but  it  is  best  not  to 
attempt  to  gain  this  information,  whicli  in  most  cases  is  of  little  practical 
importance.  The  sensation  obtained  from  palpating  the  vein  may  be  mis- 
leading in  consequence  of  the  periphlebitis,  or  of  the  soft  character  of  the 
thrombus.  Certainly,  in  view  of  the  manifest  danger  of  detaching  an  em- 
bolus, only  the  gentlest  manipulations  are  permissible.  If  the  thrombosed 
vein  be  superficial,  it  may  sometimes  be  seen  as  a  line  of  livid  redness  beneath 
the  skin.    It  is  not  always  tender  on  palpation. 

The  great  and  usually  the  only  danger  from  peripheral  thrombosis  is  fatal 
pulmonary  embolism.  It  occurs  oftenest  between  the  second  and  fourth 
weeks,*  but  may  occur  earlier  or  later.  The  danger  may  be  considered  to  be 
past  at  the  end  of  six  weeks,  if  the  local  symptoms  have  subsided ;  altliough 
there  are  exceptional  instances  of  pulmonary  embolism  at  a  later  period. 
It  is  to  l)e  noted  that  pulmonary  embolism  may  result  from  latent  and  mild 
forms  of  venous  thrombosis  as  well  as  from  those  of  the  well-marked  ex- 
amples; it  is,  however,  rare  with  the  cachectic  thromboses  of  tuberculosis 
and  cancer.  Small  pulmonary  emboli  usually  cause  no  lesions  or  symptoms, 
yet  they  may  give  rise  to  hacmorrhagic  infarction,  or  embolic  pneumonia. 

Nervous  phenomena  are  sometimes  so  prominent  as  to  have  led  to  the 
recognition  of  a  neuralgic  type  of  phlebitis  (Graves,  Trousseau,  Quenu). 
There  may  be  even  a  mild  peripheral  neuritis  associated  ^v^th  the  venous 
thrombosis.     This  is  probably  caused  by  the  direct  action  of  inflammatory 


THROMBOSIS  177 

irritants  spreading  from  tJie  inflamed  veins;  but  it  has  also  been  attributed 
to  thrombosis  of  small  veins  in  the  nerve-tnmks,  to  the  bathing  of  the  nerves 
in  the  edematous  fluid,  and  to  reflex  irritation.  Occasional  sequels  of 
femoral  thrombosis,  for  the  most  part  very  rare,  are  varicose  veins,  leg  ulcers, 
persistent  chronic  oedema,  elephantiasis,  muscular  hypertrophy,  muscular 
atrophy,  and  club-foot. 

There  has  been  much  discussion  on  the  possibility  of  gangrene  being 
caused  by  thrombosis  of  the  femoral  or  iliac  veins.  Cases  have  been  reported 
in  which  no  other  cause  of  the  gangrene  was  found  than  venous  thrombosis ; 
but  with  peripheral  venous  thrombosis  this  is  such  an  exceptional  occurrence 
that  it  seems  clear  that,  when  gangrene  results,  complicating  factors — such 
as  arterial  disease,  pressure  upon  arteries,  arterial  spasm,  great  feebleness  of 
the  circulation  or  septic  inflammation — must  be  associated  with  venous 
thrombosis.  It  is  true  that  surgeons  are  familiar  with  gangrene  after  ligation 
of  the  femoral  vein,  but  here  also  the  result  is  exceptional  and  attributable 
to  some  complication.  Braune,  upon  anatomical  grounds,  attempted  to 
demonstrate  that  gangrene  is  to  be  expected  after  closure  of  the  femoral  vein 
near  Poupart's  ligament,  but  the  clinical  evidence  does  not  support  tliis  view. 
Galliard  has  reported  a  case  and  has  collected  from  the  records  others  in 
M'hich  gangrene  had  followed  venous  without  arterial  thrombosis. 

The  thromboses  of  the  upper  extremities  are  usually  of  shorter  duration 
and  milder  type  than  those  of  the  lower;  unless  referable  to  some  persistent 
cause,  such  as  the  pressure  of  a  tumour.  They  are  often  accompanied  by 
some  cervical  oedema. 

Thrombosis  of  the  Inferior  Vena  Cava. — Since  the  days  of  Eichard  Lower 
occlusion  of  the  inferior  vena  cava  has  been  the  subject  of  much  experi- 
mental and  clinical  study.  There  are  reports  of  at  least  140  cases  of  this 
affection  in  human  beings.  The  principal  records  are  cited  in  the  mono- 
graphs of  Vimont  and  Thomas,  although  the  bibliography  is  by  no  means 
complete.  Thrombosis  of  this  vein  is  rarely  autochthonous.  Usually  it  is 
continued  from  the  femoral  or  pelvic  veins  through  the  iliacs,  or  is  due  to 
some  abdominal  disease,  as  the  pressure  of  a  tumour.  It  may  occur  without 
any  symptoms  or  without  symptoms  suggestive  of  the  diagnosis.  The  char- 
acteristic symptoms  are  oedema  of  both  lower  extremities  and  of  the  abdom- 
inal walls,  and  the  development  of  a  typical  collateral  circulation.  When 
the  renal  veins  are  likewise  occluded  there  may  be  albuminous,  bloody  urine ; 
but  with  thrombosis  of  these  veins  this  symptom  is  oftener  lacking  than 
present.  The  diagnosis  rests  especially  upon  the  appearance  of  dilated 
anastomosing  veins  coursing  upwards  from  the  groins  and  flanks  over  the 
abdominal  walls  and  lower  part  of  the  tliorax.  These  tortuous,  varicose  veins, 
sometimes  as  big  as  the  little  finger,  make  a  very  striking  and  characteristic 


178  THROMBOSIS 

picture.  The  superficial  veins  concerned  in  carrying  on  the  collateral  circu- 
lation are  the  inferior  and  superior  superficial  epigastric,  the  long  thoracic, 
the  superficial  circumflex  iliac,  the  external  pudic,  the  lumbo-vertebral 
anastomotic  trunk  of  Braune  and  numerous  unnamed  anastomotic  veins. 
The  direction  of  the  circulation  is  of  course  from  below  upward.  In  addition 
there  is  a  deep  collateral  circulation  through  various  visceral  veins  with 
dilatation  of  the  azygos  veins.  Sometimes  the  circulation  is  almost  wholly 
through  the  deep  collaterals,  and  there  may  be  little  or  no  dilatation  of  the 
visible  superficial  veins.  In  fact,  in  not  a  few  cases,  by  the  absence  of 
visible  dilated  collaterals,  the  diagnosis  is  rendered  difficult  or  impossible. 
Schlesinger  has  observed  and  collected  a  number  of  cases  where  the  oedema 
was  in  one  leg  only.  This  may  be  due  to  the  previous  establishment  of  a 
collateral  circulation  on  one  side  from  a  former  iliac  thrombosis,  or  to 
unilateral  iliac  thrombosis  with  parietal  thrombosis  of  the  vena  cava,  or  to 
congenital  duplication  of  the  vena  cava. 

Thromhosis  of  the  Renal  Veins. — This  affection  is  fairly  common.  It 
may  be  an  extension  of  a  thrombotic  process  in  the  vena  cava,  or  on  the 
other  hand  the  latter  may  be  secondary  to  renal  thrombosis.  Marantic 
thrombosis  of  the  renal  veins  is  not  unusual  in  infants  with  cerebral  symp- 
toms, or  exhausted  by  diarrhroa.  In  adults  thrombosis  of  the  renal  veins  is 
observed  not  very  infrequently  in  chronic  Bright's  disease,  particularly  the 
waxy  kidney;  and  in  malignant  tumour  of  the  kidney.  The  renal  veins  rank 
among  those  predisposed  to  marantic  thrombosis.  I  once  made  an  autopsy 
on  a  case  of  primary  genito-urinary  tuberculosis  in  which  a  caseous  mass 
had  broken  into  a  renal  vein  which  contained  an  adherent  grayish-red 
thrombus  extending  into  the  vena  cava.  Tubercle  bacilli  were  present  in 
the  caseous  mass  and  the  thrombus.  There  was  acute  miliary  tuberculosis. 
The  lesions  and  symptoms  which  one  would  expect  to  find  with  thrombosis 
of  the  main  trunk  of  the  renal  vein  are  oftener  absent  than  present.  The 
various  collateral  veins,  communicating  through  the  capsule  and  along  the 
ureters  with  the  lumbar,  diaphragmatic,  adrenal,  spermatic,  and  other  veins, 
suffice  for  adequate  return  flow.  Still  a  number  of  cases  have  been  observed 
with  more  or  less  ha?maturia  and  albuminuria  which  have  been  referred  to 
thrombosis  of  one  or  botli  renal  veins,  and  genuine  luemorrhagic  infarction 
may  occur. 

Thrombosis  of  the  Mesenteric  Veins. — Thrombosis  of  veins  in  the  intes- 
tinal wall  is  often  associated  with  ulcers  and  other  morbid  conditions  in 
the  intestine.  The  thrombus  may  extend  into  the  small  mesenteric  veins, 
or  the  latter  may  be  attacked  independently.  These  small  thrombi  are 
important  chiefly  as  a  source  of  infective  emboli  transported  to  the  liver. 

ThromlK)sis  of  the  large  mesenteric  veins  is  less  frequent  than  embolism 
or  thrombosis  of  the  mesenteric  arteries.     I  have  reported  an  instance  of 


THROMBOSIS  179 

this  affection,  and  have  found  reports  of  31  additional  cases  with  pronounced 
symptoms,  and  of  a  few  cases  without  symptoms  referable  to  the  thrombus 
and  without  intestinal  lesion.  The  references  will  be  found  at  the  end  of 
this  article.  The  superior  mesenteric  vein  was  thrombosed  much  oftener 
than  the  inferior.  In  many  cases  with  symptoms,  the  thrombosis  was  ascend- 
ing and  secondary  to  inflammation,  ulceration  or  some  other  disease  of  the 
intestine ;  in  some  instances  it  was  descending  from  thrombosis  of  the  portal 
or  splenic  vein ;  in  a  few  it  was  secondary  to  enteric  fever  or  some  marasmic 
or  cachectic  state;  in  one  it  was  attributed  to  a  calcific  plate  adjacent  to  the 
vein,  and  in  one  it  followed  splenectomy.  The  symptoms  are  the  same  as 
with  occlusion  of  the  mesenteric  arteries  (see  art.  "  Embolism,"  p.  237),  but 
as  a  rule  are  even  more  violent  in  character  and  rapid  in  course.  Tliey  are 
as  follows:  sudden  onset  of  very  intense,  colicky,  not  definitely  localised 
abdominal  pain ;  distended,  tender,  tympanitic  abdomen ;  vomiting,  which 
may  be  bloody;  obstipation  or  bloody  diarrhoea ;  and  rapid  collapse  with  cold 
sweat  and  subnormal  temperature.  The  diagnosis  is  likely  to  be  acute  ileus, 
and  laparatomy  to  be  performed.  Death  generally  occurs  within  two  or 
three  days.  The  symptoms  may,  however,  be  less  violent,  and  the  coujse  less 
rapid  than  those  mentioned.  At  the  autopsy  are  found  haemorrhagic  infarc- 
tion and  gangrene  of  the  intestine,  haemorrhages  in  the  mesentery,  bloody 
fluid  in  the  peritoneal  cavity,  and  sometimes,  although  not  regularly,  peri- 
tonitis. The  cases  without  symptoms  have  been  usually  thromboses  of  slower 
formation,  but  this  does  not  appear  to  have  been  always  the  case. 

In  a  case  reported  by  Dr.  Rolleston,  the  superior  mesenteric  vein  was 
filled  with  softened,  canalised  clot;  and  in  addition  the  inferior  mesenteric 
vein,  the  internal  and  external  iliac  veins  on  both  sides,  and  the  splenic  vein 
were  completely  thrombosed,  and  a  partly  occluding  thrombus  extended  into 
the  portal  vein.  The  thrombus  in  the  superior  mesenteric  vein  was  regarded 
as  the  oldest.  There  was  old  and  recent  inflammation  of  the  intestine,  but 
no  intestinal  infarction. 

Of  interest  is  the  relation  of  thrombosis  of  the  mesenteric  veins  to  portal 
thrombosis.  In  several  instances  of  the  latter  thrombosis  of  the  mesenteric 
veins  occurred  without  hsmorrbagic  infarction  of  the  intestine.  Doubtless 
the  explanation  is  that  a  sufficient  collateral  circulation  had  been  established 
after  the  portal  tlirombosis  to  prevent  the  usual  effects  of  a  subsequent 
mesenteric  thrombosis.  That  tliis,  however,  is  not  always  the  case  is  sho^vTi 
by  the  sudden  or  more  gradual  termination  of  some  instances  of  portal 
thrombosis  with  haemorrhagic  infarction  of  the  intestine,  in  consequence  of 
the  extension  of  the  thrombus  into  mesenteric  veins.  This  has  occurred 
especially  in  the  more  acute  cases  of  portal  thrombosis,  but  it  may  occur  also 
in  those  of  several  months'  duration.     Acute  portal  thrombosis  may  cause 


180  THROMBOSIS 

hfemorrlia^c  infarction  of  tlie  intestine  witliout  mesenteric  thrombosis;  or 
the  infarction  may  be  over  a  larger  extent  of  intestine  than  corresponds  to 
the  thrombosed  mesenteric  veins.  On  the  other  hand,  the  infarcted  area  may 
be  much  smaller  than  that  supplied  by  the  thrombosed  vein.  The  symptoms 
may  be  of  slower  development  and  of  milder  type  when  thrombosis  of  the 
mesenteric  veins  is  secondary  to  portal  thrombosis  than  when  it  is  primary. 
The  sequence  of  events  in  Fitz's  case  is  interesting — globular  thrombi  in 
the  left  ventricle,  embolism  and  infarction  of  the  spleen,  secondary  throm- 
bosis of  the  splenic  vein,  extension  of  the  thrombus  into  the  superior  mesen- 
teric vein,  hamiorrhagic  infarction  of  the  intestine  terminating  fatally. 
There  was  no  obstruction  in  the  mesenteric  arteries. 

Pylethrombosis. — The  septic  variety  of  thrombosis  of  the  portal  vein 
(suppurative  pylephlebitis)  having  been  described  (Allbutt's  "  System  of 
Medicine,"  I,  p.  610,  and  V,  p.  127),  it  remains  to  speak  here  of  simple 
portal  thrombosis,  often  called  without  much  propriety  adhesive  pylephle- 
bitis. This  is  a  well-characterised,  although  usually  not  readily-diagnosed 
affection.  It  is  caused  most  frequently  by  compression  either  of  the  intra- 
hepatic branches  of  the  portal  vein  in  cirrhosis,  syphilis,  or  tumours  of  the 
liver ;  or  of  the  main  branches  or  trunk  by  fibrous  perihepatitis,  chronic  peri- 
tonitis, swollen  lymph-glands,  impacted  gall-stones  or  tmnours.  Other 
causes  are  diseases  of  the  walls  of  the  portal  vein,  either  primary  or  propa- 
gated from  some  neighbouring  focus;  extension  of  a  thrombus  from  the 
splenic  or  mesenteric  veins;  pancreatic  disease;  gastric  cancer;  ulcer,  or 
other  gastric  or  intestinal  disease;  infective  and  toxic  diseases;  puerperal 
eclampsia  (Sclmiorl)  ;  marasmus,  and  traumatism.  Sclerosis  and  calcifica- 
tion of  the  wall  of  the  portal  vein  deserve  more  attention  as  causes  of  portal 
thrombosis  than  they  have  usually  received.  To  the  12  cases  collected  by 
Spiegelberg  and  Bomnan  in  which  this  was  the  cause,  is  to  be  added  A.  A. 
Smith's  case,  in  which  I  made  the  autopsy.  There  was  extensive  calcifica- 
tion and  thrombosis  of  both  splenic  and  portal  veins  in  a  man  about  60  years 
old,  who  died  of  gastric  hsemorrhage.  He  had  previously  vomited  blood  on 
several  occasions.  There  was  rapidly  increasing  ascites.  Calcification  of  the 
media  of  the  portal  vein  may  occur  without  marked  affection  of  the  intima. 
^larantic  portal  thrombosis  is  very  rare,  and,  according  to  Schiippel,  occurs 
chiefly  as  a  tenniiial  event  without  characteristic  symptoms.  Nonne,  how- 
ever, in  reporting  a  case  of  marantic  thrombosis  from  Erb's  clinic,  interprets 
several  previously  reported  instances  with  marked  symptoms  as  belonging 
to  this  variety.  The  thrombus  may  become  organised  and  tbe  vein  converted 
into  a  fibrous  cord,  as  in  a  case  reported  by  Osier. 

The  symptoms  are  those  of  portal  obstruction — ascites,  ha'matemesis  and 
onterorrhagia,  splenic  enlargement,  dilatation  of  superficial  abdominal  veins, 


THROMBOSIS  181 

and  progressive  marasmus.  The  caprices  of  venous  thrombosis  are  evident 
here  as  elsewhere.  Characteristic  symptoms  may  be  entirely  lacking,  or  one 
or  more  of  the  important  S3'mptoms  may  be  absent.  Ascites  has  been  absent 
or  slight,  especially  in  cases  vs^ith  abundant  hgemorrhages  from  the  stomach 
and  bowels.  In  general,  however,  the  rapid  onset,  the  intensity  of  the  evi- 
dences of  portal  obstruction,  and  especially  the  quick  return  of  ascites  after 
tapping  are  characteristic  of  obliterating  portal  thrombosis ;  and  by  observa- 
tion of  these  points  a  correct  diagnosis  has  repeatedly  been  made.  These 
acute  symptoms  are  of  most  diagnostic  \'ialue  when  they  appear  in  persons 
previously  in  apparent  health,  as  has  been  observed  with  phlebosclerotic 
thrombosis ;  or  in  the  course  of  some  disease  not  itself  a  cause  of  obstruction 
to  the  portal  circulation.  When,  as  in  cirrhosis  of  the  liver,  the  symptoms 
unfold  tliemselves  gradually,  the  diagnosis,  is  manifestly  impossible,  or  at 
best  no  more  than  mere  conjecture. 

I  have  added  traumatism  as  a  possible  cause  of  portal  thrombosis  on  the 
basis  of  a  diagnosis  made  by  Dr.  Delafield,  while  I  was  resident  physician  in 
his  service  at  Bellevue  Hospital.  A  lad,  who  had  received  a  severe  blow  on 
the  abdomen,  was  admitted  with  extreme  ascites  which  had  come  on  within 
two  weeks  after  the  injury.  He  was  repeatedly  tapped,  the  clear  fluid  re- 
accumulating  at  first  with  great  rapidity  after  each  tapping,  afterward 
more  slowly,  until  in  the  course  of  months  there  was  complete  recovery.  In 
the  meantime  enlarged  veins  made  their  appearance  over  the  upper  part  of 
the  abdomen. 

Jaundice  is  not  a  symptom  of  portal  thrombosis,  although  repeatedly 
observed  as  a  complication.  The  channels  for  establishment  of  a  collateral 
circulation  are  the  same  as  in  cirrhosis  of  the  liver,  with  the  exclusion  of 
those  which  communicate  with  the  portal  vein  itself,  at  or  beyond  the  site  of 
occlusion. 

Under  certain  exceptionally  favourable  conditions  recovery  may  take  place; 
a  satisfactory  collateral  circulation  being  established,  with  perhaps  opening 
of  channels  through  the  organised  thrombus.  The  usually  fatal  termination 
may  be  from  haemorrhage  or  exhaustion,  sometimes  within  a  few  weeks  or 
even  days  from  the  onset.  I  know  of  no  instance,  in  man,  of  death  within 
a  few  hours  after  occlusion  of  the  portal  vein,  such  as  occurs  regularly, 
Avith  great  fall  of  arterial  blood-pressure,  after  ligating  this  vessel  in  rabbits 
and  dogs.  As  already  mentioned,  heemorrhagic  intestinal  infarction  may 
be  caused  by  portal  thrombosis  (pp.  179  and  180), 

There  has  been  much  discussion  on  the  occurrence  of  changes  in  the 
liver  which  can  be  attributed  directly  to  stoppage  of  the  portal  circulation. 
In  the  majority  of  cases  of  portal  thrombosis  the  liver  has  been  the  seat  of 
atrophic  cirrhosis,  but  most  modern  authors  have  regarded  the  thrombosis 


182  THROMBOSIS 

as  secondary  to  the  cirrhosis.  Dr.  Samuel  West,  however,  in  1878,  took 
strong  ground  in  favour  of  the  reverse  being  sometimes  the  case;  and  he 
found  support  in  the  experimental  results  of  Solowieff.  The  later  experi- 
ments of  Cohnheim  and  Litten  have  been  widely  accepted  as  indicating  that 
obstruction  of  the  portal  vein  is  without  effect  upon  the  hepatic  structure 
and  functions.  Bermant  has  recently  gone  over  the  entire  experimental 
and  anatomico-clinical  evidence,  and  has  reached  the  conclusion  that  stop- 
page of  the  portal  vein  may  lead  to  atrophic  cirrhosis.  The  case  which  he 
reports  speaks  strongly  in  favour  of  this  view;  for  only  the  right  branch 
of  the  portal  vein  was  thrombosed,  and  the  cirrhosis  was  limited  to  the 
corresponding  lobe  of  the  liver.  Nevertheless,  cases  of  portal  thrombosis, 
some  not  of  short  duration,  have  been  reported  by  Frerichs,  Leyden,  Alex- 
ander, and  others  without  any  alteration  in  the  liver;  and  I  have  observed 
two  such  cases  in  which  the  symptoms  of  portal  obstruction  extended  over 
several  months." 

Thrombosis  of  the  Splenic  Vein. — Primary  thrombosis  of  the  splenic  vein 
and  its  radicles  is  rare.  I  have  seen  an  instance  oi  autochthonous  tlirombosis 
secondary  to  calcification  of  the  wall  of  the  splenic  vein.  Thrombosis  of 
veins  within  the  spleen,  extending  sometimes  into  the  main  trunk,  is  com- 
mon with  infarction,  abscess,  and  certain  other  morbid  processes  in  this 
organ.  Thrombosis  of  the  main  trunk  may  be  caused  by  suppurative  or 
haemorrhagic  pancreatitis,  or  by  cancer  of  the  pancreas.  As  has  already 
been  mentioned,  thrombi  may  extend  from  the  portal  or  mesenteric  veins  into 
tlie  splenic,  as  well  as  from  the  latter  into  the  former.  There  is  the  possi- 
bility of  thrombosis  secondary  to  retrograde  embolism  of  the  splenic  vein. 

Koster  has  reported  the  rare  complication  of  enteric  fever  with  tlirombosis 
of  the  radicles  and  main  trunk  of  the  splenic  vein ;  the  evidence  being  conclu- 
sive that  the  oldest  part  of  the  thrombus  was  in  the  spleen.  The  evidences 
of  occlusion  of  the  main  vein  appeared  at  the  beginning  of  convalescence. 
The  spleen  was  enormously  swollen  and  the  pulp  of  a  diffuse  reddish-black 
colour.  The  capsule  and  surrounding  tissues  were  suffused  with  blood.  As 
there  were  thrombi  in  the  small  mesenteric  veins  near  the  ulcerated  ileum, 
there  was  a  possibility  of  retrograde  embolism;  but  Koster  thinks  it  more 
probable  that  the  process  originated  within  the  spleen. 

Thrombosis  limited  to  the  extra-splenic  part  of  the  vein  may  be  com- 
pletely or  nearly  compensated  by  the  collateral  venous  circulation,  so  that 
no  cliaiigcs  or  only  a  moderate  passive  congestion  occur  in  the  spleen. 

"Chiari  (Centralh.  f.  allR.  Path.  u.  path.  Anat.  1898,  IX,  p.  854)  has  recently 
described  endophlebitis,  with  thrombosis,  of  the  radicles  of  the  hepatic  vein. 
There  were  symptoras  of  portal  obstruction. 


THROMBOSIS  183 

Thrombi  occupying  intrasplenic  veins  may  cause  haemorrhagic  infarc- 
tion. Dr.  Eolleston  has  observed  two  instances  of  anaemic  infarcts  of  the 
spleen  in  association  with  thrombosis  of  the  splenic  vein.  Litten  probably 
goes  too  far  in  attributing  most  genuine  haemorrhagic  as  distinguished  from 
pale  infarcts  of  the  spleen,  to  venous  thrombosis  rather  than  to  arterial 
embolism. 

Extensive  necrosis  and  haemorrhagic  infarction  may  be  caused  by  torsion 
of  the  pedicle  of  a  movable  spleen.  A  perhaps  unique  instance  of  this  occur- 
rence was  observed  in  the  Johns  Hopkins  "Hospital,  aiid  has  been  described 
by  Osier. 

Obliteration  of  tlie  Superior  Vena  Cava. — Since  the  admirable  studies  by 
Duchek  (1854)  and  by  Oulmont  (1856)  of  the  causes  and  symptoms  of 
obliteration  of  the  superior  vena  cava  a  considerable  number  of  instances 
of  this  condition  have  been  reported.  By  far  the  most  frequent  cause  is 
the  pressure  of  a  mediastinal  tumour,  of  swollen  lymph-glands,  or  of  an 
aneurysm.  Less  common  is  the  growth  of  a  cancer  or  other  malignant 
tumour  into  the  lumen  of  the  vein.  Banti  reports  a  curious  case  of  general- 
ised tuberculosis  in  which  nearly  the  whole  length  of  the  superior  vena  cava 
was  completely  filled  by  a  neoplastic  tuberculous  mass  projecting  into  the 
right  auricle.  The  outer  walls  of  the  vein  were  intact.  The  condition  seems 
to  have  been  analogous  to  the  tuberculous  cardiac  thrombi  already  described 
(p.  142).  Primary  thrombosis  of  the  superior  vena  cava  is  so  rare  as  to 
be  a  pathological  curiosity.  Poynton  has  reported  an  instance  of  thrombotic 
occlusion  of  the  upper  two-thirds  of  the  superior  vena  cava  in  association 
with  chronic  and  acute  valvular  endocarditis,  and  in  a  second  case  of  val- 
vular disease  he  found  a  mural  thrombus  in  this  vein.  In  both  cases  there 
was  tricuspid  insufficiency  (pp.  157  and  158).  The  characteristic  symptoms 
are  oedema  and  cyanosis  of  the  upper  half  of  the  body — face,  neck,  arms  and 
thorax — and  dilatation  of  deep  and  superficial  veins,  especially  marked  over 
the  anterior  wall  of  the  thorax  and  upper  part  of  the  abdomen.  In  a  case 
exhibited  by  Dr.  Osier  to  the  Johns  Hopkins  Hospital  Medical  Society,  the 
anterior  surface  of  the  chest  was  covered  with  large,  spongy  bunches  of  enor- 
mous varicose  veins,  in  one  of  which  a  phlebolith  could  be  felt.  Other  symp- 
toms, which  may  be  present,  are  oedema  of  conjunctival  and  buccal  mucous 
membranes,  exophthalmos,  watery  secretion  from  the  conjunctivae,  nose- 
bleeding,  and  such  signs  of  venous  congestion  of  the  brain  as  headache, 
vertigo,  and  ringing  in  the  ears,  especially  on  bending  over.  In  the  light 
of  the  whimsicalities  of  venous  thrombosis  it  is  hardly  necessary  to  add 
that  the  symptoms  may  be  less  marked,  and  may  deviate  from  what  miglit 
naturally  be  expected. 


184  THROMBOSIS 

Thrombosis  of  the  Innomiriafe,  Subclavian,  and  Jugular  Veins. — The 
more  important  literature  of  tliis  subject  is  cited  in  the  papers  of  Pohl, 
Hirsclilaff,  and  Helen  Baldwin.  The  occurrence  of  these  thromboses  in 
cardiac  disease,  and  from  compression,  has  already  been  mentioned  (pp.  157 
and  158) ;  other  rare  causes  are  infection,  empyema,  acute  rheumatism,  tuber- 
culosis, marasmus,  and  traumatism.  The  symptoms  are  the  usual  ones  of 
venous  congestion,  cedematous  swelling,  pain  in  the  regions  from  which  the 
veins  convey  blood,  dilatation  of  collaterals,  and  in  the  case  of  the  cervical 
veins,  recognition  of  the  thrombosed  vein  by  palpation,  which,  however, 
should  be  done  with  great  care. 

Thrombosis  of  the  pulmonary  veins  may  be  mentioned  as  a  rare  source  of 
embolism  in  the  aortic  system.  It  is  usually  secondary  to  some  pulmonary 
disease,  as  gangrene,  malignant  tumours,  abscess,  infarction,  tuberculosis, 
pneumonia.  It  has  been  observed  with  extensive  emphysema  of  the  lungs 
(Schmale). 

Thrombosis  of  the  cerebral  sinuses  will  be  considered  in  connection  with 
diseases  of  the  brain  in  the  following  volume.  (Allbutt's  Syst.  Med., 
Vol.  VIII.) 

0.  Wyss  has  described  a  remarkable  instance  of  extensive  haemorrhagic 
myelitis  caused  by  widespread  hyaline  and  platelet  thrombi  in  veins  within 
the  spinal  cord.  The  thrombosis  was  secondarv-  to  a  glioma  of  the  dorsal 
cord.  Rosin  has  likewise  observed  thrombosis  of  veins  extending  the  whole 
length  of  the  spinal  cord,  consecutive  to  a  tumour  of  the  cervical  cord. 

Multiple  Thromboses. — Finally  may  be  mentioned  the  cases  in  which 
many  veins  in  different  parts  of  the  body  become  thrombosed,  as  in  Iluels's 
case  of  chlorotic  thrombosis ;  and  Osiers,  of  thrombosis  secondarv'  to  cancer 
of  the  stomach,  already  cited  (pp.  IGO  and  156).  Erlenmeyer  has  described 
as  "jumping  thrombosis"  (springende  Thrombose),  in  distinction  from 
the  ordinary  creeping  form,  cases  in  whicli  tlie  process  attacks  first  one  vein 
and  tben  another,  in  a  different  region,  until  finally  various  veins  in  tlie 
extremities,  trunk,  and  brain  may  become  plugged. 

TuKAT.MKNT. — The  treatment  of  thrombosis  of  the  extremities  is  about 
all  that  needs  special  consideration  in  this  article.  In  view  of  the  part  played 
by  enfeebled  circulation  and  secondary  infections  in  the  causation  of  throm- 
bosis, prophylactic  measures  should  bo  directed  toward  maintaining  good 
nutrition,  strengthening  the  heart's  action,  and  warding  off  secondary  infec- 
tion, so  far  as  may  be,  or  treating  accessible  foci  of  infection  antiseptically. 

In  the  a])senfe  of  any  available  medir-inal  treatment  known  to  have  any 
direct  control  over  tbe  process  of  tlirombosis,  tlie  general  indications  for 
treatment  are  to  secure  as  speedily  as  possible  an  adequate  collateral  cir- 
culation, in  onlcr  to  ward  off  tbc  danger  of  tissue-necrosis  or  gangrene  from 


THROMBOSIS  185 

arterial  thrombosis  and  the  effects  of  passive  congestion  from  venous  throm- 
bosis; and,  above  all,  in  the  case  of  venous  thrombosis,  to  guard  against 
the  detachment  of  emboli.  These  indications  are  best  met  by  absolute  rest, 
suitable  position  and  immobilisation  of  the  thrombosed  extremity,  and 
nourishing  diet. 

With  venous  thrombosis  of  a  lower  extremity  the  patient  should  lie  on  the 
back  with  the  limb  elevated  on  an  inclined  plane,  or  in  a  trough  well  lined 
with  cotton  wool.  The  limb  should  be  kept  warm  by  wrapping  in  cotton 
wadding,  and  hot  fomentations  of  lead-water  and  laudanum,  or  some  simi- 
lar preparation,  may  be  applied.  If  the  condition  of  the  heart  indicate  it, 
digitalis  or  other  cardiac  tonic  may  be  given.  At  the  height  of  the  process 
the  pain  may  be  so  intense  as  to  require  the  use  of  opium  or  some  of  its 
derivatives. 

It  is  all-important  to  know  what  not  to  do.  The  patient  should  be  cau- 
tioned against  moving  the  leg,  especially  against  any  sudden  jerk.  Palpa- 
tion of  the  affected  veins  should  be  of  the  gentlest  sort  and  is  better  omitted 
altogether.  All  unnecessary  movements  and  manipulations  should  be 
avoided.  Nothing  is  gained,  and  harm  may  be  done  by  resorting,  before 
all  danger  of  embolism  is  passed,  to  the  old-fashioned  treatment  of  rubbing 
in  mercurial  or  belladonna  ointment.  The  length  of  time  that  the  patient 
should  remain  quiet  in  bed  will  vary  according  to  tiie  severity  of  the  case. 
Although  the  thrombotic  process  does  not  usually  progress  after  the  tenth 
or  twelfth  day,  it  is  a  general  rule  that  the  patient  should  not  be  allowed 
to  walk  in  less  than  forty  days.  A  large  number  of  the  deaths  from  pul- 
monary embolism  have  occurred  when  the  patient  first  walks,  or  goes  to 
stool,  or  takes  a  bath. 

Light  bandaging  of  the  lower  part  of  the  leg  assists  the  circulation ;  but, 
if  applied  at  all,  it  should  be  with  only  minimal  compression.  After  the 
danger  of  embolism  is  passed,  massage  and  bandaging  may  be  employed 
to  advantage,  or  a  long  elastic  stocking  worn. 

If  gangrene  result  from  arterial  thrombosis,  the  time  and  site  of  opera- 
tion should  be  determined  upon  surgical  principles. 

REFETRENCES 

The  references  are  only  to  authors  cited  in  the  text,  and  are  not  intended  to 
be  a  complete  bibliography  of  the  subject.  The  references  to  authors  cited  under 
different  headings  in  the  text  will  usually  be  found  only  under  the  first  heading 
in  which  the  reference  appears. 

Stbucti^re  of  Thrombi 

1.  Arnold:    Virchow's  Archiv,  1897,  I.  p.  445. 

2.  Bizzozero:    Virchow's  Arch.,  1882,  XC,  p.  261. 

3.  Determann:    XVI.  Congr.  f.  inn.  Med.,  1898,  p.  237. 

15 


186  THROMBOSIS 

4.  Eberth  and  Schimmelbusch:    Die  Thrombose  nach  Versuchen  u.  Leichenbe- 

funden.    Stuttgart,  1888. 

5.  Hammersten:    Ztschr.  f.  physiol.  Chem.,  1896-97,  XXII,  p.  333. 

6.  Hanau:    Fortschr.  d.  Med.,  1886,  IV,  p.  385. 

7.  Hayem:    Compt.  rend,  de  I'Acad.  des  sc,  July  18,  1882. 

8.  Klebs:    Allg.  Path.  Th.  II,  Jena,  1889. 

9.  Kriege:    Virch.  Arch.,  1889,  CXVI,  p.  64. 

10.  Lowit:    Arch.  f.  exp.  Path.  u.  Pharm.,  1887,  XXIII,  p.  1,  and  XXIV,  p.  188. 

11.  Lubnitzky:    Arch.  f.  exp.  Path.  u.  Pharm.,  1885,  XIX,  p.  185. 

12.  Mantegazza:    Gazz.  med.  lombard.,  1869. 

13.  Mosso:    Virch.  Arch.,  1887,  CIX,  p.  205. 

14.  Muller,  Fr.:     Ziegler's  Beitr.,  1898,  XXIII,  p.  498. 

15.  Osier:    Seguin's  Arch,  of  Med.,  Feb.,  1881. 

16.  Idem:  Centralbl.  f.  med.  Wiss.,  July  29,  1882. 

17.  Idem:   Cartwright  Lectures,  1886. 

18.  Pitres:    Arch.  d.  phys.  norm,  et  path.,  1876,  p.  230. 

19.  von  Recklinghausen:     Handb.  d.  allg.  Path.  d.  Kreislaufs  u.  d.  Ernahrung. 

Stuttgart,  1893. 

20.  Ribbert:    Die  path.  Anat.  u.  d.  Heil.  d.  durch  Staph,  pyog.  aur.  hervorgeruf. 

Erkrank.     Bonn,  1891. 

21.  Virchow:    Gesammelte  Abhandlungen.    Frankf.,  1856. 

22.  Weigert:    Virchow's  Archiv,  1877,  LXX,  p.  483,  and  1880,  LXXIX,  p.  87. 

23.  Idem:  Thrombose,  in  Eulenburg's  Real-Encyclopadle. 

24.  Welch:     The   Structure    of  White    Thrombi,   Trans.    Path.    Soc.    of   Phila- 

delphia, 1887,  XIII. 

25.  Welch  and  Clement:     Remarks  on  Hog  Cholera  and   Swine  Plague,   Proc. 

30th  Annual  Convention,  U.  S.  Vet.  Med.  Assoc,  etc.,  Chicago,  1893. 

26.  Wlassow:    Ziegler's  Beitrage,  1894,  XV,  p.  543. 

27.  Zahn:    Virchow's  Arch.,  1875,  LXII,  p.  81. 

28.  Zenker,  K.:    Ziegler's  Beitr.,  1895,  XVII,  p.  448. 

29.  Ziegler:    Lehrb.  d.  allg.  Path.  u.  spec.  path.  Anat,  9te  Aufl.,  Bd.,  I,  p.  149. 

Growth,  Metamorphoses,  and  Obqanisation 

30.  Aschoff:    Virch.  Arch.,  1892,  CXXX,  p.  93. 

31.  Beneke:    Ziegler's  Beitr.,  1890,  VII,  p.  95. 

32.  Legg,  Wickham:    Tr.  Path.  Soc.  Lond.,  1878,  XXIX,  p.  50. 

33.  Thoma:    Lehrb.  d.  path.  Anat,  I,  Stuttgart,  1894. 

34.  Zahn:    Virchow-Festschrift.  Internat.  Beitr.,  II,  p.  199. 

Etiology 

35.  Balllie,   Matthew:     Trans.   Soc.   Improvement  Med.   and   Chir.   Knowledge, 

1793,  I,  p.  119. 

36.  Baumgarten:    D.  sogen.  Organisation  d.  Thrombus,  Leipz.,  1877. 

37.  Beugnies-Corbeau:    Gaz.  med.  de  Li6ge,  1890,  p.  348. 

38.  Birch-Hirschfeld:    Congr.  inn.  Med.,  1892,  p.  28. 

39.  Brodie  and  Russell:    Journal  of  Physiol.,  1897,  Nos.  4-5. 

40.  Briicke:    Brit  and  For.  Med.-Chir.  Rev.,  1857,  XIX,  p.  183. 

41.  Cohnheim:    Vorles.  iib.  allg.  Path.,  Bd.,  I,  Berl.,  1882. 

42.  Cruveilhier:    Anat  path.,  Paris,  1829-42. 


THROMBOSIS  187 

43.  Davy,  John:    Researches,  Physiological  and  Anatomical,  London,  1839. 

44.  Denys:    Centralbl.  f.  allg.  Path.  u.  path.  Anat.,  1893,  IV,  p.  174. 

45.  Eguet:    Mitth.  a.  Klin.  u.  med.  Inst.  d.  Schweiz,  1894,  II,  Hft.  4. 

46.  van  Emden:    Fortschr.  d.  Med.,  1898,  XVI,  pp.  241  and  281. 

47.  Ehrlich  and  Lazarus:    Die  Anamie,  1.  Abth.  Wien,  1898. 

48.  Flexner:    Journ.  Exp.  Med.,  1896,  I,  p.  559. 

49.  Freund:    Wien.  med.  Blatter,  1886,  p.  296. 

50.  Idem:  Wiener  med.  Jahrb.,  1888,  p.  259. 

51.  Glenard:    Contrib.  a  I'etude  des  causes  de  la  coag.  spontan.  du  sang.    These. 

Paris,  1875. 

52.  Groth:     Ueb.    d.    Schicksale    farbloser    Blutkoorperchen,   etc.      Inaug.-Diss. 

Dorpat,  1884. 

53.  Halliburton:    Journal  of  Physiol.,  1893,  XIII,  p.  806;   XV,  p.  90,  and  (with 

Pickering)  XVIII,  p.  285. 

54.  Hayem:    Du  sang  et  de  ses  alterations  anatomiques.    Paris,  1889. 

55.  Hayem:    Wien.  med.  Zeit.,  1897,  Nos.  17-19. 

56.  Hunter,  John:     Obs.   on  the  Inflam.   of  the   Intern.  Coat  of  Veins,   Trans. 

Soc.  Improvement  Med.  and  Chir.  Knowledge,  1793,  I,  p.  18. 

57.  Kohler:    Ueb.  Thrombose  u.  Transfusion.  Inaug.-Diss.  Dorpat,  1877. 

58.  Laennec:    De  I'auscult.  mediate,  etc.    Paris,  1819. 

59.  Landois:    Die  Transfusion  d.  Blutes.     Leipz.,  1875. 

60.  von  Limbeck:    Prag.  med.  Woch.,  1890,  XV,  pp.  351,  365. 

61.  Mallory:    Journ.  of  Exp.  Medicine,  1898,  III,  p.  611. 

62.  Maragliano  and  Castellino:    Ztschr.  f.  kl.  Med.,  1892,  XXI,  p.  415. 

63.  Martin,  C.  J.:    Journal  of  Physiology,  1893,  XV,  p.  380. 

64.  Muir:    Journal  of  Anatomy  and  Physiology,  1890-91,  XXV. 

65.  Naunyn:    Arch.  f.  exp.  Path.  u.  Pharm.,  1873,  I,  p.  1, 

66.  Paget:    St.  Barth.  Hosp.  Rep.,  1866,  II,  p.  82. 

67.  Ponfick:    Deutsche  Klinik,  1867,  Nos.  20-26. 

68.  Idem:  Virch.  Arch.,  1874,  LX,  p.  153. 

69.  Idem:  Virch.  Arch.,  1875,  LXII,  p.  273. 

70.  Ranke:    D.  Blutvertheilung  u.  d.  Thatigkeltswechsel  d.  Organe.    Leipz.,  1891. 

71.  Sahli:    Centralbl.  f.  inn.  Med.,  1894,  p.  497. 

72.  Schimmelbusch:     Ueb.    Thrombose  im   gerinnungsunfahigen  Blute.   Inaug.- 

Diss.     Halle,  1886. 

73.  Silbermann:    Virch.  Arch.,  1889,  CXVII,  p.  288. 

74.  Singer:    Arch.  f.  Gynak.,  LVI,  p.  218. 

75.  Tiirk:    Klin.  Untersuch.  lib.  d.  Verhalten  d.  Blutes  bei   Infectionskrankh. 

Wien,  1898. 

76.  Vaquez:    De  la  thrombose  cachectique.     These.    Paris,  1890. 

77.  Idem:   De  la  phlebite,  in  Clin.  med.  de  la  Charite,  Paris,  1894,  p.  751. 

78.  Weigert:    Fortschr.  d.  Med.,  1887,  V,  p.  231. 

79.  Widal:   Etude  sur  I'infection  puerperale.    These.    Paris,  1889. 

80.  Wooldridge:    On  the  Chemistry  of  the  Blood  and  other  Scientific  Papers. 

Arranged  by  Victor  Horsley  and  Ernest  Starling.    Lond.,  1893. 

Localisation 

81.  Arnold:    Ziegler's  Beitr.,  1890,  VIII,  p.  29. 

82.  Benivieni:    De  abditis  nonnullis  ac  mirandis  morborum  et  sanationum  causis. 

Florent,  1507. 


188  THROMBOSIS 

83.  Birch-Hirschfeld:    Deutsch.  med.  Woch.,  1892,  p.  267. 

84.  Bostroem:    Deutsch.  Arch.  f.  kl.  Med.,  1895,  LV,  p.  219. 

85.  Burns,  Allan:    Obs.  on  some  of  the  most  frequent  and  important  diseases  of 

the  heart.     Edinb.,  1809. 

86.  zum    Busch:     Ueb.    d.    Zusammensetzung    d.    Herzthromben.      Inaug.-Disa. 

Freiburg,  I,  B.,  1891. 

87.  van  der  Byl:    Tr.  Path.  See,  Lond.,  1858,  IX,  p.  89. 

88.  Choisy  and  Nuhn:    Cited  from  No.  93. 

89.  Czapek:    Prager  med.  Woch.,  1891,  XVI,  p.  458. 

90.  Delgpine:    Tr.  Path.  Soc,  Lond.,  1890,  XLI,  p.  43. 

91.  Ewart  and  Rolleston:    Tr.  Clin.  Soc,  Lond.,  1897,  XXX,  p.  190. 

92.  Haga:    Virch.  Arch.,  1898,  CLII,  p.  26. 

93.  Hertz:    Deutsch.  Arch.  f.  kl.  Med.,  1885,  XXXVII,  p.  74. 

94.  Hoegerstedt  and  Nemser:    Ztschr.  f.  kl.  Med.,  1896,  XXXI,  p.  130. 

95.  Hutchinson,  Jonathan:    Arch,  of  Surg.  Apr.,  1898,  p.  100. 

96.  Krumbholz:    Arb.  a.  d.  med.  Klinik  zu  Leipzig,  1893,  p.  328. 

97.  Krumm:    Deutsch.  Arch.  f.  kl.  Med.,  1895,  LIV,  p.  189. 

98.  Lancereaux:    Traite  d'anat.  path,  t,  I,  p.  604.    Paris,  1875-77. 

99.  Kotlar:   Prag.  med.  Woch.,  1894,  XIX,  pp.  78  and  97. 

100.  Legg,  Wickham:    Tr.  Path.  Soc,  Lond.,  1878,  XXIX,  p.  49. 

101.  Macleod:    Edinb.  Med.  Journ.,  Feb.,  1883,  p.  696. 

102.  Manteuffel,  Zoege.  von:    Deutsch.  Ztschr.  f.  Chir.,  1898,  XLVII,  p.  461. 

103.  Ogle:    Tr.  Path.  Soc  Lond.,  1868.  XIV,  p.  127. 

104.  Osier:    Johns  Hopkins  Hospital.  Rep.,  1890,  II,  p.  56. 

105.  Idem:  Montreal  Med.  Journ.,  1897,  XXV,  p.  729. 

106.  Parmentier:    Arch.  gen.  de  med.,  July,  1889. 

107.  Pawlowski:    Ztschr.  f.  kl.  Med.,  1894,  XXVI,  p.  482. 

108.  von  Recklinghausen:    No.  19,  and  Deutsch.  Arch.  f.  kl.  Med.,  1885,  XXXVII, 

p.  495. 

109.  Redtenbacher:    Wien.  kl.  Woch.,  1892,  V,  p.  688. 

110.  Rosenbach:     Die  Krankh.  d.  Herzens,  Hft..  I,  p.  180.     Wien  u.  Leipz.,  1893. 

111.  Stange:    Arb.  a.  d.  path.  Inst.  z.  Gottingen,  1893,  p.  232. 

112.  Voelcker:   Tr.  Path.  Soc  Lond.,  1893,  XLIV,  p.  31. 

113.  Wagner:    Arch.  d.  Heilk.,  1861,  II,  p.  364. 

114.  Weichselbaum:    Cited  from  No.  83. 

115.  Wertheimer:    Arch,  de  physiol.,  1895,  5.  S.,  VII,  p.  107. 

116.  von  Winiwarter:    Arch.  f.  kl.  Chir.,  1878,  XXIII. 

117.  Wood.  William:    The  Edinburgh  Med.  and  Surg.  Journ.,  1814,  K,  p.  50. 

118.  Zahn:    Virch.  Arch.,  1889,  CXV,  p.  55. 

119.  V.  Ziemssen:    Congr.  f.  inn.  Med.,  1890,  p.  281. 

AssociATio.N  WITH  Certain  Diseases 
Enteric  Fever 

120.  Boinet  and  Romary:    Arch.  d.  m6d.  exp.,  1897.  IX,  p.  902. 

121.  Carbone:   Gaz.  med.  di  Torino,  1891,  No.  23. 

122.  Crocq:    Arch.  d.  m6d.  exp.,  1894,  VI,  p.  583. 

123.  Gilbert  and  Lion:    Bull,  m6d..  1889,  p.  1266. 

124.  Girode:     Bull,  m^d.,  1889,  p.  1392. 

125.  Haushalter:    Mercredi  m6d.,  Sept.  20,  1893. 


THROMBOSIS  189 

126.  Holscher:    Miinch.  med.  Woch.,  1891,  pp.  43,  62. 

127.  Keen :    Surgical  Complications  and  Sequels  of  Typhoid  Fever.    Philadelphia, 

1898.     (Consult  for  other  references  to  Arterial  Thrombosis  in  Enteric 
Fever. ) 

128.  Rattone:    Morgagni,  1887,  XXIX,  p.  577. 

129.  Vincent:    Mercredi  med.,  Feb.  17,  1892. 

130.  Viti:    Atti  d.  r.  Accad.  d.  fisiocrit.  di  Siena,  1890,  4.  S.,  II,  p.  109. 

Influenza 

131.  Baumler:    Congr.  f.  inn.  Med.,  1890,  p.  305. 

132.  Chaudet:    La  phlebite  grippale.    Paris,  1892. 

133.  Chiari:    Prager  med.  Woch.,  1890,  p.  124. 

134.  Guttmann  and  Leyden:    Die  Influenza-Epidemie,  1889-90.     Wiesbaden,  1892. 

135.  Klebs:    Deutsch.  med.  Woch.,  1890,  p.  278. 

136.  Kuskow:    Virch.  Arch.,  CXXXIX,  p.  406. 

137.  Lasker:    Inaug.-Diss.    Freiburg,  1897. 

138  Leichtenstern :    In  Nothnagel's  Spec.  Path.  u.  Therap.,  Bd.,  IV,  Th.,  II,  Abth., 
I.    Wien,  1896. 

139.  Leyden:   Charite-Annalen,  XVII,  and  XVIII. 

140.  Rendu:    Bull,  med.,  1892,  pp.  50,  296. 

Pneumonia 

141.  Barbanceys:   Etudes  sur  la  coag.  d.  sang  dans  les  veines.    These.    Paris,  1870. 

142.  Blagden:    St.  Barth.  Hosp.  Journ.,  1897-98,  V,  p.  122. 

143.  Da  Costa:    Philadelphia  Med.  Journ.,  1898,  II,  p.  519. 

144.  Dickinson,  Lee:   Brit.  Med.  Journ.,  1896,  I,  p.  149. 

145.  Fabries:    Sem.  med.,  1888,  p.  144. 

146.  Laache:    Deutsch.  med.  Woch.,  1893,  p.  785. 

147.  Leyden:    Centralbl.  f.  in.  Med.,  1887,  p.  25. 

148.  Osier:    The  principles  and  Practice  of  Medicine,  p.  124.     New  York,  1898. 

149.  Traite  de  medecine,  t.  V,  pp.  374,  432. 

(For  other  references  to  arterial  and  venous  thrombosis  in  pneumonia.) 

Acute  Articular  Rheumatism 

150.  Gatay:   Contrib.  a  I'etude  de  la  phlebite  rhumatismale.    These.    Paris,  1895. 

151.  Legroux:    Gaz.  hebd.  de  med.,  1884,  p.  140. 

152.  Schmitt:    De  la  phlebite  rhumatismale.    These.    Paris,  1884. 

Appendicitis 

153.  Mynter:    Appendicitis  and  its  Surgical  Treatment,  Philadelphia,  1897. 

Tuberculosis 

154.  Blumer:    Amer.  Journ.  Med.  Sc,  1898,  II. 

155.  Dodwell:    Am.  Journ.  Med.  Sc,  1893,  I,  p.  641. 

156.  Flexner:    Johns  Hopkins  Hosp.  Bull.,  1891,  p.  120. 

157.  Hektoen:    Journ.  Exp.  Med.,  1896,  p.  112. 

158.  Hirtz:    Mercredi  med.,  1894,  No.  40. 


190  THROMBOSIS 

159.  Michaelis  and  Blum:    Deutsche  med.  Woch.,  1898,  p.  550. 

160.  Stroebe:    Centralbl.  f.  allg.  Path.  u.  path.  Anat..  1897,  p.  998. 

161.  Sabrazes  and  Mongour:    Rev.  med.  de  Test,  1897,  p.  306. 

Cachectic  States 

162.  Charcot:    Union  med.,  1865,  XXVI,  p.  165. 

163.  Gouget:    Bull,  de  la  soc.  anat,  1894,  No.  13. 

164.  Pitres,  Bitot,  and  Regnier:    Cited  from  No.  77. 

165.  von  Recklinghausen:    No.  19. 

166.  RigoUet:    De  la  phlebite  paludeene.    These.     Bordeaux,  1891. 

Cardiac  Incompetency 

167.  Baldwin,  Helen:    Journ.  Am.  Med.  Assoc,  1897,  August  21,  p.  371. 

168.  Cohn:    Klinik  d.  embol.  Gefasskrankh.    Berlin,  1860. 

169.  Cheadle  and  Lees:    Lancet,  1898,  H,  p.  206  (reported  by  Poynton). 

170.  Hirschlaff:     Inaug.-Diss.     Berlin,  1893. 

171.  Huchard:    Rev.  gen.  de  clin.  et  de  therap.,  1897,  XI,  p.  787. 

172.  Kahn  (and  Hanot) :    Arch.  gen.  de  med.,  1896,  II,  p.  469. 

173.  Mader:    Jahrb.  d.  Wien.  k.-k.  Krankenanst,  1895,  1897,  IV,  p.  252. 

174.  Nicolle:   Normandie  m6d.,  1897,  XII,  p.  68. 

175.  Ormerod:    Tr.  Path.  Soc.  Lond.,  1889,  XL,  p.  75. 

176.  Ramirez:    Gaz.  med.  de  Paris,  1867,  No.  47,  p.  716. 

177.  Robert:    Bull,  de  la  soc.  anat.,  1880,  V,  p.  314. 

Chlorosis 

178.  Ball:    Trans.  Assoc.  Amer.  Physicians,  1889,  IV,  p.  52. 

179.  von  Noorden:     In   Nothnagel's   Spec.   Path.   u.   Therap.    Bd.,   VI If,   Th.,    II. 

Wien,    1897. 

180.  Schweitzer:    Virchow's  Arch.,  1898,  CLII,  p.  337. 

(The  three  preceding  articles  contain  the  principal  references  to 
chlorotic  thrombosis.  The  following  Nos.  181  to  192  are  the  references 
to  cases  not  found  in  them.) 

181.  Audry:    Lyon  m6d.,  1892  and  1893. 

182.  Dickinson,  Lee:    Tr.  Clin.  Soc.  Lond.,  1896,  XXIX,  p.  63. 

183.  Duckworth  and  Buzzard:    Brit.  Med.  Journ.,  1896,  I,  p.  149. 

184.  Gagnoni:    Riforma  med.,  1897,  XIII,  p.  472. 

185.  Guinon:    Bull,  et  m6m.  soc.  med.  des  hop.  de  Paris,  1896,  XII,  p.  297. 

186.  Gutheil:    Inaug.-Diss.     Freiburg,  1892. 

187.  Hayem:    Bull.  m6d.,  1896,  p.  261. 

188.  Powell,  Douglas:    Lancet,  1888,  II.  p.  1124. 

189.  Dr.  Thayer's  case  was  of  a  chlorotic  young  woman  with  thrombosis  of  left 

femoral,  iliac  and  uterine  veins.     Death  from  pulmonary  embolism. 

190.  Vaquez:    No.  77. 

191.  Vergely:    Bull.  m6d.,  1889,  p.  1175. 

192.  Villard:    Assoc,  frang.  pour  I'avancement  des  sciences,  1891,  II,  p.  791.    Paris, 

1892. 

193.  Buttersack:    Ztschr.  f.  kl.  Med.,  1897,  XXXIII.  p.  456. 
193a.  Sankey,  W.:    Ed.  Med.  and  S.  Journ.,  1814,  p.  401. 


THROMBOSIS  191 

Gouty,  Idiopathic  and  Primary  Infective  Thrombosis 

194.  Barbe:    La  France  med.,  1898.   (Syphilis). 

194a.  Daguillon:    Contrib.  k  I'etude  clin.  de  la  phlebite  primitive.    Th^se.    Paris. 
1894. 

195.  Dowse:    Lancet,  1879,  II,  p.  268. 

196.  Osier:    Trans.  Assoc.  Amer.  Physicians,  1887,  II,  p.  135. 

197.  Paget:    No.  66. 

198:  Tuckwell:    St.  Barth.  Hosp.  Rep.,  1874,  X,  p.  23. 

Effects  and  Symptoms 
Cardiac,  Arterial,  and  Capillary  Throvihosis 

199.  Barth:    Deutsch.  med.  Woch.,  1896,  p.  269. 

200.  Blachez:    Gaz.  des  hop.,  1866,  No.  13, 

201.  Bristowe:    Tr.  Path.  Soc.  Lond.,  1870,  XXI,  p.  143. 

202.  Charcot:    Compt.  rend.  soc.  de  biol.,  1858,  Paris,  1859,  2.  S.,  V,  pt.  2,  p.  225. 

203.  Chiari:    Prager  med.  Woch.,  1897,  Nos.  6,  7. 

204.  Gerhardt:    Wurzburg.  med.  Ztschr.  Bd.,  IV,  and  V. 

205.  Heidenhain:    Deutsch.  med.  Woch.,  1891,  p.  1087. 

206.  Kidd,  Percy:    Tr.  Path.  Soc.  Lond.,  1886,  XXXVII,  p.  197. 

207.  Marie,  R.:  L'infarctus  du  myocarde  et  ses  consequences.     Paris,  1897. 

208.  Naunyn:    In  Nothnagel's  Spec.  Path.  u.  Ther.  Bd.,  VII,  Th.,  VI,  p.  216.    Wien, 

1898. 

209.  Pitt,  Newton:    Tr.  Path.  Soc.  Lond.,  1893,  XLIV,  p.  52. 

210.  Porter:    Journ.  Exp.  Medicine.  1896,  I,  p.  46. 

211.  Welch:    In  Pepper's  System  of  Medicine,  II,  p.  505. 

212.  von  Ziemssen:    No.  119. 

Venous  Thrombosis 

213.  Cohnheim:    Vorles.  iib.  allg.  Path.  Bd.,  I,  pp.  150,  492. 

214.  Cohnstein:    In  Lubarsch-Ostertag's  Ergebnisse,  1896,  II,  p.  563.    Wiesbaden, 

1897.     (Consult  for  literature  on  theories  of  oedema.) 

215.  Galliard:    Med.  moderne,  1894,  V,  p.  861. 
261.  Hamburger:    Virch.  Arch.,  1895,  CXLI,  p.  398. 

217.  Lazarus-Barlow:    Phil.  Trans.  Roy.  Soc,  CLXXXV,  B.,  1894,  p.  779. 

218.  Idem:  A  Manual  of  General  Pathology.    London,  1898. 

219.  Loschner:    Prager  med.  Woch.,  1888,  No.  22. 

220.  Schlesinger:    Deutsch.  med.  Woch.,  1896,  p.  460. 

221.  Starling:    Lancet,  1896,  I,  p.  1407. 

222.  Thomas:     Beitr.    z.    Differ .-Diagnostik   zwischen    Verschluss    d.    Pfortaders 

u.  d.  unteren  Hohlvenen,  Bibliotheca  medica,  Cassell,  1895. 

223.  Vimont:    Contrib.  k  I'etude  des  obliterations  de  la  veine  cave  infer.     These. 

Paris,  1890,  p.  224. 

224.  Welch:    Journ.  of  Exp.  Med.,  1896,  I  p.  35. 

225.  Koster:    Deutsch.  med.  Woch.,  1898,  p.  325. 

(This  and  the  papers  cited  by  K.  contain  references  to  16  cases  of 
thrombosis  of  mesenteric  veins.  The  additional  cases  with  symptoms  are 
Nos.  226  to  239.) 


192  THEOMBOSIS 

226.  Barth:    Bull,  med.,  1897,  Oct.  27,  p.  989. 

227.  Boucly:    Th^se.     Paris,  1884. 

228.  Burgess:    Sheffield  Med.  Journ.,  1892-93,  I,  p.  317  (3  cases). 

229.  Delatour:    Annals  of  Surgery,  1895,  XXI,  p.  24. 

230.  Fltz:    Trans.  Ass.  Amer.  Phys.,  1887,  II,  p.  140. 

231.  Garmsen:    Inaug.-Diss.    Kiel,  1895. 

232.  Leech:    Quart.  Med.  Journ.,  Sheffield,  1897-8,  VI,  p.  370. 

233.  Lilienthal:    Matthew's  Quart.  Journ.  Rectal,  etc.,  Louisville,  1898,  V,  p.  158. 

234.  Lund:     Hospitalstidende,  Mar.  23,  1898. 

235.  M'Weeny:    Lancet,  Dec.  23,  1893. 

236.  Nordenfeldt:    Hygiea,  1897,  LIX,  pt.  2,  p.  228. 

237.  Smith:    Dublin  Journ.  of  Med.  Sc,  1894,  XCVII,  p.  274. 

238.  Watson:    Boston  Med.  and  Surg.  Journ.,  1894,  CXXXI,  p.  556. 

239.  Westhoff:    Inaug.-Diss.  Kiel,  1895. 

(Cases  without  symptoms  are  reported  in  Nos.  240-243.) 

240.  Cohn:    Embolische  Gefasskrankh. 

241.  Frerichs:   Klinik  d.  Leherkrankh. 

242.  Rolleston:    Trans.  Path.  Soc,  London,  1892,  XLIII,  p.  49. 

243.  Spiegelberg:    Virchow's  Arch.,  CXLII,  p.  547. 

244.  Baldwin,  Helen:    J.  Amer.  Med.  Assoc,  1897,  XXIX,  p.  371. 

245.  Banti:    Sperimentale,  1891,  p.  408. 

246.  Bermant:     Ueb.   Pfortaderverschluss   u.    Leberschwund.    Inaug.-Diss.,   1897. 

247.  Borrmann:    Deutsch.  Arch.  f.  kl.  Med.,  1897,  LIX,  p.  283. 

248.  Conheim  and  Litten:    Virch.  Arch.,  1876,  LXVII,  p.  153. 

249.  Duchek:    Viertl.  Jahrs.  f.  d.  prakt.  Heilk,  1854,  XLI,  p.  109. 

250.  Erlenmeyer:    Deutsch.  med.  Woch,  1890,  p.  781. 

251.  Hirschlaff:    Inaug.-Diss.,  Berlin,  1893. 

252.  Litten:    In  Nothnagel's  Spec.  Path.  u.  Therap.  Bd.,  VIII,  Th.,  Ill,  p.  41. 

253.  Nonne:    Deutsch:  Arch.  f.  kl.  Med.,  1885,  XXXVII,  p.  24L 

254.  Osier:    Johns  Hopkins  Hosp.  Bull.,  1891,  II,  p.  40. 

255.  Idem:  Journ.  Anat.  and  Physiol.,  1878,  XXIX,  p.  107. 

256.  Oulmont:    Soc.  m6d.  d'observ.,  Paris,  1855,  III,  pp.  361,  468. 

257.  Pohl:    Inaug.-Diss.     Gottingen,  1887. 

258.  Rolleston:    Trans.  Path.  Soc.  London,  1892,  XLIII,  p.  49. 

259.  Rosin:    Verhandl.  d.  XVI  Congr.  f.  innere  Medicin,  1898,  p.  415. 

260.  Schiippel:    In  Ziemssen's  Handb.  d.  spec.  Path.  u.  Therap.,  Bd.,  VIII,  I.  2, 

p.  279. 

261.  Schmale:    Ueber  Thrombose  d.  Pulmonalvenen  bei  Emphysem,    Inaug.-Diss. 

Wurzburg,  1889. 

262.  Smith.  A.  A.:    N.  Y.  Med.  Journ.,  1880,  XXXI,  p.  16. 

263.  Solowieff:    Virch.  Arch.,  1875,  LXII,  p.  195. 

264.  West:    Tr.  Path.  Soc.  London,  1878,  XXIX,  p.  107. 

265.  Wyss,  0.:    Verhandl.  d.  XVI  Congr.  f.  innere  Medicin,  1898,  p.  399. 

266.  Bennett,  Wm.  H.:    The  relations  of  thrombosis  to  varix   (Lancet,  1898,  II, 

p.  973). 


EMBOLISM ' 

Definition. — Embolism  is  the  impaction  in  some  part  of  the  vascular 
system  of  any  undissolved  material  brought  there  by  the  blood-current. 
The  transported  material  is  an  embolus.  Embolism  may  occur  likewise  in 
lymphatic  vessels. 

Historical  Note. — Rudolf  Virchow  is  the  creator  of  the  doctrine  of 
embolism.  There  is  scarcely  another  pathological  doctrine,  of  equal  magni- 
tude, the  establishment  of  which  is  so  largely  the  work  of  a  single  man. 
Kot  but  that  there  were  foreshadowings  of  this  conception  before  Virchow, 
notably  by  Bonetus  and  van  Swieten  in  the  seventeenth  and  eighteenth 
centuries,  and  by  Allibert  and  Frangois  in  the  early  part  of  the  present  cen- 
tury. A  few  observers  and  experimenters,  indeed,  anticipated  some  of  Vir- 
chow's  results.  The  wonder  is  that  until  Virchow's  time  the  idea  of  embolism 
remained  so  foreign  to  medical  thought;  so  obvious  and  necessary  a  corollary 
does  it  seem  to  be  of  the  discovery  of  the  circulation  of  the  blood.  Between 
the  years  1846  and  1856  Virchow  constructed  the  whole  doctrine  of  embol- 
ism upon  the  basis  of  anatomical,  experimental  and  clinical  investigations, 
which  for  completeness,  accuracy,  and  just  discernment  of  the  truth  must 
always  remain  a  model  of  scientific  research  in  medicine.  These  discoveries 
introduced  new  chapters  and  necessitated  a  recasting  of  many  old  ones  in 
pathology.  A  number  of  important  morbid  conditions,  among  which  pul- 
monary embolism  and  cerebral  embolism  may  be  especially  mentioned,  were 
now  for  the  first  time  clearly  recognised.  Virchow's  studies  of  thrombosis 
and  his  demonstration  that  not  all  intravascular,  ante-mortem  clots  are 
formed  at  the  place  where  they  are  found,  and  that  infarcts  are  not  the 
result  of  inflammation  and  capillary  phlebitis,  put  an  end  to  the  false  and 
to  us  at  present  almost  incomprehensible  ideas  then  prevailing  as  to  the 
overshadowing  importance  of  phlebitis  in  pathological  processes.  Especially 
was  the  doctrine  of  metastasis,  which  in  old  days  was  one  of  the  most 
mystical  in  medicine,  greatly  expanded  and  at  the  same  time  placed  upon  an 
intelligible  and  firm  foundation. 

The  new  fields  opened  by  Virchow  have  been  industriously  cultivated 
by  a  multitude  of  workers.  The  additions  to  our  knowledge  have  been  many 
and  valuable,  but  they  have  related  mainly  to  details,  and  can  scarcely  be 
said  to  have  led  to  new  points  of  view.     The  works  of  Bernhard  Cohn  and 

>  In:    Syst.  Med.  (Allbutt),  Lond.,  1899,  VII,  228-285. 
193 


194  EMBOLISM 

of  Cohnheim  may  be  signalised  as  among  the  most  important  of  the  con- 
tributions since  Virchow's  early  publications.  Cohn's  remarkable  book, 
published  in  1860,  is  extraordinarily  rich  in  anatomical,  experimental,  and 
clinical  facts,  and  it  is  well  for  any  one  who  believes  that  he  has  a  new  obser- 
vation or  opinion  concerning  embolism  to  consult  it  before  venturing  on 
publication ;  a  precaution  which  has  evidently  been  often  neglected  by 
writers  on  the  subject. 

Varieties  of  Emboli, — Substances  of  the  most  varied  character,  solid, 
liquid  or  gaseous,  may  enter  the  circulation  and  be  conveyed  as  emboli. 
Unless  some  special  epithet  be  used,  an  embolus  is  generally  understood 
to  be  a  detached  thrombus,  or  part  of  it,  including  under  this  designation 
endocarditic  vegetations.  Other  possible  sorts  of  emboli  are  fragments  of 
diseased  heart-valves,  calcific  masses,  bits  of  tissue,  tumour-cells,  paren- 
chymatous cells,  animal  or  vegetable  parasites,  fat,  air,  pigment-granules 
and  foreign  bodies.  Emboli  of  air,  of  fat,  and  of  parenchymatous  cells 
will  be  considered  separately.  An  im})ortant  classification,  as  regards 
their  effects,  is  into  bland  or  aseptic  emboli  and  toxic  or  septic  emboli. 

Sources  of  Emboli. — Emboli  in  the  lungs  come  from  the  systemic 
veins,  the  right  heart  or  the  pulmonary  artery;  those  in  branches  of  the 
portal  vein  come  from  the  radicles  or  trunk  of  this  vein;  those  in  systemic 
arteries  from  the  pulmonary  veins,  the  left  heart,  or  some  artery  between 
the  heart  and  the  location  of  the  embolus.  Sources  of  aberrant  emboli, 
resulting  from  unusual  modes  of  transportation,  will  be  considered  subse- 
quently (p.  196). 

Various  features  in  the  structure  and  disposition  of  thrombi  bearing 
upon  the  detachment  of  emboli  have  been  described  in  the  preceding  article. 
Here  may  be  especially  recalled  the  continuation  of  an  occluding  venous 
thrombus  in  the  form  of  a  partly  obstructing  thrombus  beyond  the  entrance 
of  an  important  branch,  and  the  occurrence  of  softening  in  the  interior  of 
older  thrombi ;  plienomena  evidently  favourable  to  the  detachment  of  frag- 
ments. Globular  thrombi  in  the  right  heart,  particularly  in  the  auricular 
appendix,  are  a  fruitful  source  of  the  emboli  which  cause  pulmonary  infarc- 
tion in  heart  disease.  Vegetations  of  the  aortic  and  mitral  valves,  particu- 
larly of  the  latter,  furnish  the  great  majority  of  emboli  in  the  aortic  system. 
Thrombosis  or  embolism  of  an  arterial  trunk — as  of  the  internal  carotid, 
splenic,  femoral — Ls  often  followed  by  the  conveyance  of  fragments  of  the 
plug  into  branches  of  the  artery.  When  the  plug  in  the  main  trunk  is  an 
embolus,  this  secondary  embolism  is  described  by  Cohnheim  as  "  recur- 
rent"— an  epithet  which  lias  also  been  applied  to  retrograde  embolism,  and, 
therefore,  to  avoid  confusion,  had  better  not  be  used  in  either  sense. 


EMBOLISM  195 

The  detection  of  the  source  of  an  embolus  is  often  unattended  by  any 
difficulty;  but  sometimes  it  requires  prolonged  and  painstaking  search, 
and  occasionally  even  such  a  search  is  unrewarded.  The  greatest  difficulties 
are  encountered  when  the  source  is  in  some  peripheral  venous  thrombus 
which  has  caused  no  sjiiiptoms  and  is  unattended  by  lesions  suggestive  of 
its  location.  An  entire  thrombus  may  be  dislocated  and  transported  as  an 
embolus. 

Site  of  Deposit. — Emboli  are  carried  along  by  the  blood-current  until 
they  are  caught  on  some  obstruction,  or  become  lodged  in  a  channel  too 
narrow  to  permit  their  further  passage.  It  is  evident  that  embolism  can 
scarcely  occur  except  in  the  arterial  system,  pulmonary  and  systemic,  and 
in  branches  of  the  portal  vein.  The  rare  instances  of  embolism  of  systemic 
veins  will  be  considered  under  aberrant  embolism  (p.  196).  An  extremely 
rare  occurrence,  of  which  several  instances  are  recorded,  is  the  blocking 
of  the  tricuspid  or  mitral  orifice  by  an  embolus.  The  result  is,  of  course, 
sudden  death.  Very  often  an  embolus  is  caught  at  an  arterial  bifurcation, 
which  it  rides  with  a  prolongation  extending  into  each  branch  (riding 
embolus).  This  may  happen  where  the  diameter  of  each  branch  is  greater 
than  that  of  the  embolus.  It  is  not  uncommon  for  several  emboli  to  enter 
successively  the  same  branch  of  the  pulmonary  artery. 

Any  artery  open  to  the  circulating  blood  may  receive  an  embolus  of 
appropriate  size.  The  course  followed  by  an  embolus  in  its  travels  is 
determined  by  purely  mechanical  factors,  of  which  the  most  important 
are  the  size,  form,  and  weight  of  the  plug;  the  direction,  volume,  and 
energy  of  the  carrying  blood-stream ;  the  size  of  branches  and  the  angles  at 
which  they  are  given  off;  and  the  position  of  the  body  and  its  members. 
In  accord  with  these  principles  we  find  emboli  in  the  lower  lobes  of  the 
lungs  oftener  than  in  the  upper;  and  in  the  right  lung  oftener  than  in  the 
left,  the  right  pulmonary  artery  being  larger  than  the  left.  Emboli  from 
the  left  heart  are  more  frequently  carried  into  the  abdominal  aorta  and  its 
branches  than  into  the  carotid  or  subclavian  arteries.  The  left  carotid, 
arising  directly  from  the  aortic  arch  at  its  highest  point,  is  in  more  direct 
line  with  the  aortic  blood-stream  than  is  the  right  carotid,  and  is  there- 
fore a  commoner  recipient  of  emboli.  The  left  common  iliac  artery  is  also 
somewhat  more  directly  in  the  line  of  the  current  in  the  abdominal  aorta, 
and,  therefore,  receives  emboh  somewhat  more  frequently  than  the  right. 

The  order  of  frequency  in  which  emboli  are  found  in  the  different 
arteries  may  be  given  about  as  follows: — pulmonary,  renal,  splenic,  cere- 
bral, iliac  and  the  lower  extremities,  axillary  and  upper  extremities,  coeliac 
axis  with  its  hepatic  and  gastric  branches,  central  artery  of  the  retina, 
superior  mesenteric,  inferior  mesenteric,  abdominal  aorta,  coronarj'  of  tlio 


19G  EMBOLISM 

heart.  There  is,  however,  considerable  difference  of  statement  on  this 
point.  As  a  matter  of  fact  this  list,  like  similar  ones,  does  not  inform 
us  of  the  frequency  with  which  the  different  arteries  of  the  body  receive 
emboli ;  for  it  is  evident  that  it  is  based  almost  entirely  upon  embolic 
manifestations,  and  not  upon  the  mere  presence  of  emboli.  If  estimates 
of  frequency  be  based  only  on  infective  emboli,  the  order  would  be  in 
several  respects  different,  the  hepatic  artery,  for  example,  standing  higher 
in  the  list,  and  the  cerebral  lower — sufficient  evidence  that  the  customary 
data  for  determining  the  frequency  of  embolism  in  different  arteries  relate 
only  to  such  emboli  as  leave  behind  some  record  of  their  presence.  Infec- 
tive emboli,  however,  do  not  inform  us  of  the  incidence  of  embolism  in 
different  arteries;  for  these  produce  abscesses  or  other  lesions  in  certain 
special  situations,  and  not  in  every  place  where  they  may  lodge;  a  fact 
which  is  brought  out  clearly  in  the  experimental  injections  of  bacteria 
into  the  circulation  of  animals.  It  seems  to  me  very  probable  that  of 
the  systemic  arteries,  those  going  to  the  lower  extremities  must  be  more 
frequent  receptacles  of  emboli  than  either  the  splenic  or  the  renal;  but 
the  smaller  plugs  in  the  former  usually  leave  no  readily  demonstrable 
record  of  their  presence,  whereas  in  the  latter  they  always  do. 

Aberiu-Nt  Embolism. — Certain  exceptions  to  the  general  rules  already 
stated  concerning  the  sources  and  direction  of  transportation  of  emboli 
may  be  grouped  under  the  heading  of  aberrant  or  atypical  embolism,  the 
latter  epithet  being  the  one  employed  by  Scheven  to  designate  paradoxical 
embolism,  and  retrograde  embolism. 

Zahn  gave  the  name  "  paradoxical  embolism,"  and  his  assistant  Rostan 
the  name  "  crossed  embolism,"  to  the  transportation  of  emboli  derived  from 
veins  into  the  systemic  arteries  without  passing  through  the  pulmonary 
circulation.  Cohnheim  was  the  first  to  note  the  passage  of  venous  emboli 
through  an  open  foramen  ovale  into  the  aortic  system ;  and  since  then  there 
have  been  enough  observations  of  this  so-called  paradoxical  embolism  to 
prove  tliat,  although  not  frequent,  it  is  really  of  practical  importance,  and 
not  merely  a  curiosity.  Zahn  and  Rostan  found  an  open  foramen  ovale 
in  about  ono-fifth  of  their  autopsies,  which  is  a  considerably  smaller  per- 
centage than  most  pathologists,  who  have  investigated  the  subject,  have 
found.  An  opening  in  the  form  of  an  oblique  slit  is  certainly  very  often 
present  in  the  oval  fossa  (in  34  per  cent  of  all  cases  according  to  Firket), 
and  it  has  been  demonstrated  by  actual  observation  that,  under  certain 
conditions,  this  form  of  opening  suffices  for  the  transit  of  emboli.  In 
three  cases  an  embolus  was  found  by  Zahn  and  Rostan  actually  engaged 
in  the  opening,  and  two  or  three  similar  observations  have  been  made  by 
others. 


EMBOLISM  197 

I  have  found  records  of  twenty-eight  cases  of  paradoxical  embolism, 
and  there  is  no  reason  to  suppose  that  this  list  is  complete.  The  evidence 
upon  which  the  diagnosis  is  usually  based  is  an  open  foramen  ovale  and 
the  presence  in  the  systemic  arteries  of  coarse  emboli,  for  which  the  only 
source  to  be  found  is  on  the  venous  side  or  in  the  right  auricle.  While 
in  some  of  the  cases  there  may  be  room  for  scepticism  as  to  the  venous 
origin  of  the  arterial  embolism,  there  can  be  none  for  Schmorl's  observa- 
tio'n,  in  a  case  of  traumatic  laceration  of  the  liver,  of  plugs  of  hepatic 
tissue  in  the  left  auricle  and  the  main  trunk  of  the  renal  artery,  with  an 
open  foramen  ovale  admitting  a  finger.  Conditions  favouring  the  occur- 
rence of  paradoxical  embolism  are,  according  to  Zahn,  increased  pressure 
in  the  right  auricle  and  lowered  pressure  in  the  left.  Under  these  cir- 
cumstances the  opening  in  the  oval  foramen  is  widened,  and  its  walls 
bulge  toward  the  left  auricle.  Eostan  and  Hauser  have  seen  thrombi 
extending  from  the  right  auricle  through  the  oval  foramen  into  the  left. 

The  best  explanation  of  certain  tumour  metastases  without  pulmonary 
implication  is  by  paradoxical  embolism.  Here,  however,  there  is  some- 
times another  possibility;  for,  as  Zahn  has  demonstrated,  tumour  cells 
not  of  large  size  may  pass  through  the  pulmonar}'  capillaries.  Although 
the  lungs  are  an  excellent  filter,  tlieir  capillaries  are  certainly  so  wide 
that  they  may  permit  the  transit  of  emboli  too  large  to  pass  through 
capillaries  elsewhere  in  the  body. 

The  first  conclusive  observation  of  retrograde  transport  of  an  embolus 
in  a  human  being  was  made  by  Heller,  in  1870,  who  found,  in  a  case  of 
primary  cancer  of  the  ca?cum  and  ileum,  a  loose  plug  of  cancerous  tissue 
in  a  branch  of  an  hepatic  vein.  The  only  metastatic  growths  were  in  the 
mesenteric,  retroperitoneal,  and  mediastinal  lymphatic  glands.  Long  before 
Heller,  however,  the  conception  of  retrograde  transport  of  venous  emboli 
was  familiar  to  pathologists;  especially  in  the  discussions  of  the  explana- 
tion of  metastatic  hepatic  abscesses  in  cases  where  the  lungs  are  not 
involved  and  the  atrium  of  infection  does  not  communicate  with  the  portal 
system.  The  experimental  side  of  the  subject  was  diligently  cultivated. 
The  general  trend  of  opinion  among  pathologists,  however,  was  opposed  to 
the  acceptance  of  the  doctrine  of  retrograde  transport,  under  conditions 
occurring  in  human  beings,  until  the  publication  of  von  Recklinghausen's 
article  on  the  subject  in  1885.  He  reported  a  convincing  observation  of 
embolism  of  the  renal  veins  with  masses  of  sarcoma,  derived  from  a  primary 
growth  of  the  tibia,  and  also  of  retrograde  embolism  from  the  left  auricle 
into  the  pulmonary  veins.  Since  this  publication  there  have  been  a  number 
of  equally  conclusive  demonstrations  of  the  retrograde  transport  of  venous 
emboli,  and  the  subject  has  been  taken  up  again  on  the  experimental  side. 


198  EMBOLISM 

Retrograde  venous  embolism  is  an  interesting,  but,  so  far  as  at  present 
known,  a  rare  occurrence. 

The  difficulty  of  making  sure  that  a  suspected  thrombotic  embolus  in 
a  systemic  vein  is  not  an  autochthonous  thrombus  is  doubtless  the  reason 
wliy  most  of  the  reports  of  retrograde  transport  relate  to  emboli  of  tumour- 
cells  or  parenchymatous  cells.  In  addition  to  Hellers  and  von  Reckling- 
hausen's cases  already  mentioned,  reference  may  be  made  to  Arnold's 
observation  of  masses  from  a  primary  mammary  carcinoma  filling  the 
superior  longitudinal  sinus,  with  invasion  of  the  wall  of  the  sinus  from 
within  by  the  new  growth,  but  without  any  intracranial  tumour  outside 
of  this  wall;  or  indeed  any  metastasis  elsewhere  in  the  body  except  in  the 
axillary  and  cervical  lymph-glands:  and  also  to  Ernst's  case  of  primary 
angio-sarcoma  of  the  left  kidney,  growing  into  the  renal  vein,  with  a  loose 
plug  of  sarcomatous  tissue  distending  a  branch  of  a  coronary  vein  of  the 
heart  without  connection  with  a  metastatic  growth.  Bonome's  observa- 
tion of  cancer  of  the  thyroid  with  metastatic  nodules  in  the  liver,  develop- 
ing from  plugs  in  the  hepatic  veins,  should  probably  also  be  included  in  the 
list,  as  well  as  two  cases  of  Bonome,  reported  by  Lui,  in  one  of  which  a 
cancerous  embolus  secondary  to  cancer  of  the  rectum  was  found  in  a  branch 
of  the  superior  mesenteric  vein;  and  in  the  other  a  similar  retrograde 
embolus,  secondary  to  adeno-carcinoma  of  the  liver,  was  met  with  in  the 
right  pampiniform  plexus. 

To  Sehmorl's  and  Lubarsch's  cases  of  emboli  of  liver-cells  in  the  cere- 
bral and  the  renal  veins  may  be  added  two  observations  from  my  labora- 
tory, of  which  one  has  been  reported  by  Flexner,  of  clumps  of  liver-cells 
in  branches  of  the  renal  vein  in  cases  with  extensive  hepatic  necroses. 

That  retrograde  transport  of  ordinary  venous  thrombi  may  occur,  is 
demonstrated  by  Arnold's  discovery  in  a  large  branch  of  an  hepatic  vein 
of  a  riding  embolus  identical  in  appearance  with  a  thrombus  which  occu- 
pied the  right  ovarian  vein  and  extended  some  distance  into  the  inferior 
vena  cava.  Colin  accepted,  for  a  limited  class  of  cases,  backward  convey- 
ance of  venous  emboli ;  and  in  this  sense  interprets  an  observation  of  throm- 
lK)sis  of  the  superior  longitudinal  sinus,  with  a  plug  in  the  right  axillary 
vein  identical  in  appearance  with  an  undoubted  embolus  in  the  pulmonary 
artery.  Yon  Recklinghausen  has  furnished  evidence  of  the  retrograde  trans- 
port of  infective  emboli  into  the  renal  veins. 

From  these  cases  it  is  seen  that  retrograde  embolism  of  particles  of 
tumour,  of  tumour-cells,  of  parenchymatous  cells,  and  of  ordinary  bland 
and  infective  thrombotic  fragments  has  been  observed.  Experiments  have 
demonstrated  that,  under  certain  conditions,  light  as  well  as  heavy  particles 
may  be  transported  in  the  veins  in  a  direction  contrary  to  that  of  the 


EMBOLISM  199 

normal  blood-current.  The  veins  in  which  retrograde  embolism  in  human 
beings  has  been  found  are  the  hepatic,  the  renal,  the  mesenteric,  the 
pampiniform  plexus,  the  coronary  of  the  heart,  the  cerebral  veins  and 
sinuses,  the  axillary  and  the  pulmonary.  Experimental  retrograde  em- 
bolism has  been  produced  in  many  other  veins,  including  those  of  the  lower 
extremities.  While  venous  valves,  when  intact,  are  undoubtedly  a  pro- 
tection against  this  occurrence,  they  are  often  imperfectly  developed  or 
insufficient.  Emboli  have  been  repeatedly  observed  in  the  cerebral  veins 
and  sinuses  which  should  be  protected  by  valves  in  the  jugular  veins. 

Retrograde  embolism  is  usually  explained  by  a  temporary  reflux  of  the 
venous  current  in  consequence  of  some  sudden  obstacle  to  the  return  flow 
to  the  right  heart,  as  may  occur  with  forced  expiration  and  coughing. 
Whatever  increases  the  pressure  in  the  veins  near  the  heart,  and  impairs 
the  assistance  to  the  venous  stream  afforded  by  the  respiratory  movements 
and  the  suction  of  the  right  heart,  favours  this  backward  movement. 
Increased  intrathoracic  pressure,  stenosis  of  the  respiratory  passages,  spasm 
of  respiratory  muscles,  distension  of  the  right  heart,  tricuspid  insufficiency, 
slowing  of  the  heart's  beats  from  vagus-irritation,  are  among  the  conditions 
believed  to  dispose  to  retrograde  transport. 

Eibbert  does  not  accept  the  reflux  theory  of  retrograde  embolism;  partly 
for  lack  of  any  positive  observation  of  such  backward  flow  beyond  the 
immediate  neighbourhood  of  the  right  heart,  and  partly  on  account  of  the 
difficulty  in  explaining  what  becomes  of  all  the  blood  which  would  be  momen- 
tarily pressed  back  toward  the  capillaries.  His  explanation  is  that  in  con- 
ditions of  high  venous  stasis,  eml)oli,  sticking  loosely  to  the  venous  wall, 
are  not  moved  forward  by  the  feeble  current,  but  are  slowly  pressed  back- 
ward, step  by  step,  by  pulse-waves  in  the  veins.  For  this  view  he  finds 
support  in  experiments  which  he  has  made.  Observations,  partly  experi- 
mental, of  Arnold  and  of  Ernst,  cannot  readily  be  reconciled  with  Ribbert's 
explanation;  so  that,  notwithstanding  difficulties  needing  further  elucida- 
tion, the  reflux  theory  seems  at  present  the  more  probable  for  most  cases. 

Of  a  different  nature  from  the  preceding  form  of  retrograde  transport 
is  the  conveyance  of  emboli  by  a  blood-current  reversed  from  its  normal 
direction  in  consequence  of  obstruction  of  veins  by  compression  or  other 
causes.  This  kind  of  retrograde  transport  from  more  or  less  permanent 
reversal  of  the  normal  current  is  far  more  frequent  in  lymphatic  vessels 
than  in  veins,  and  plays  an  important  part  in  the  metastases  of  tumours 
by  means  of  the  lymphatics. 

Anatomical  Characters. — The  appearances  observed  in  cmbolised  ves- 
sels vary  with  the  shape,  size,  consistence,  and  nature  of  the  embolus,  and 
the  duration  of  its  impaction.    Approximately  spherical  emboli,  as  a  rule, 


200  EMBOLISM 

completely  close  the  lumen  of  the  artery  in  which  they  lodge.  Cylindrical, 
elongated,  or  flat  emboli  are  usually  caught  as  riders  at  an  arterial  bifur- 
cation; and  often  at  first  leave  more  or  less  of  the  channels  by  their  side 
open.  Thrombi  several  inches  long  may  be  washed  out  of  the  femoral  or 
other  peripheral  vein.  Such  a  transported  thrombus  may  be  found  in  the 
trunk  or  a  primary  division  of  the  pulmonary  artery,  folded  two,  three, 
or  even  four  times  upon  itself,  and  pressed  at  different  points  into  several 
of  the  main  arterial  branches  at  the  hilum  of  the  lung,  as  in  an  interesting 
case  described  by  Fagge.  In  this  way  an  embolus  may  completely  plug 
a  vessel  three  or  four  times  its  diameter.  Irregularly-shaped  emboli,  if  of 
soft  consistence,  may  be  pressed  into  an  artery  so  as  to  block  the  lumen 
completely ;  but  if  of  firmer  consistence  they  leave  at  first  some  space  for  the 
blood  to  flow.  Emboli  may  be  of  such  consistence  as  to  be  shattered  by 
impact  with  the  arterial  wall,  the  fragments  blocking  many  or  all  of  the 
small  branches,  and  producing  the  same  effect  as  if  the  plug  had  been 
arrested  in  the  main  trunk. 

An  embolus  is  the  starting-point  of  a  secondary'  thrombus  which  usually, 
although  not  always,  completes  the  closure  of  the  vessel,  if  this  was  not 
effected  by  the  embolus  itself,  and  extends  on  each  side  to  the  nearest 
branch.  The  same  metamorphoses  and  process  of  organisation,  with  con- 
secutive changes  in  the  vascular  wall,  occur  with  emboli  and  encapsulating 
thrombi,  as  described  in  the  previous  article  for  primary  thrombi.  Non- 
absorbable emboli  or  parts  of  emboli,  like  foreign  bodies,  are  encapsulated 
by  cells  and  tissue. 

In  cases  of  recent  embolism,  the  plug  can  generally  be  recognised  as  an 
embolus  without  much  difficulty ;  but,  in  those  of  long  standing,  the 
anatomical  diagnosis  between  embolism  and  thrombosis  may  be  difficult, 
or  even  impossible.  The  criteria  for  the  recognition  of  a  fresh  embolus 
are  for  the  most  part  sufficiently  self-evident.  Such  a  plug  lies  loosely  or 
is  but  slightly  adherent  to  the  vessel-wall.  It  often  presents  a  broken  or 
fractured  surface  which,  in  fortunate  cases,  may  be  made  to  fit  on  the 
corresponding  surface  of  the  thrombus  from  which  it  was  originally  broken 
off.  It  may  be  i)ent  or  folded,  or  show  the  marks  of  venous  valves,  or 
present  ramifications  wliich  do  not  correspond  to  those  of  the  artery  in 
which  it  lies.  It  is  of  course  of  the  first  imjwrtance  to  find,  if  possible, 
the  source  of  the  embolus ;  and,  when  this  is  done,  to  make  a  careful  com- 
parison between  the  thrombus  and  the  embolic  fragment  as  to  resemblances 
in  structure  and  a[)[)oarance. 

After  the  embolus  ha.s  bcH-ome  adherent  and  surrounded  by  a  secondary 
thrombus,  some  of  these  differential  criteria  may  still  remain  for  a  while; 
but,  as  time  passes,  the  anatomical  diagnosis  becomes  increasingly  difficult. 


EMBOLISM  201 

The  embolus  may  perliaps  still  be  distinguished  from  the  surrounding 
thrombus  by  marked  differences  in  its  age  and  general  appearance  and 
structure,  possibly  by  the  presence  of  lime  salts.  An  adherent  plug 
which  rides  an  arterial  bifurcation  is  much  more  likely  to  be  an  embolus 
than  a  primary  thrombus.  In  reaching  a  conclusion,  weight  must  be 
given  to  the  condition  of  the  arterial  wall;  whether  there  be  any  local 
cause  for  thrombosis, — such  as  compression,  aneurysm,  arterio-sclerosis ; 
and  whether  the  microscope  shows  such  secondary  changes  in  the  arterial 
wall  as  generally  correspond  to  the  apparent  age  and  character  of  the 
adherent  plug.  The  detection  of  a  source  for  an  embolus  will  be  an 
important  consideration.  The  clinical  history  may  aid  in  the  antomical 
diagnosis ;  and  all  attendant  circumstances,  especially  the  existence  else- 
where of  undoubted  emboli,  should  be  taken  into  consideration.  In  some 
situations,  as  in  branches  of  the  renal  or  splenic  arteries,  primary  throm- 
bosis is  so  uncommon  that  the  chances  are  all  in  favour  of  embolism. 

It  is  evident  from  what  has  been  said  tliat  in  the  older  cases  the  anatomi- 
cal diagnosis  must  often  be  based  upon  a  weighing  of  probabilities,  and 
that  sometimes  a  positive  conclusion  cannot  be  reached. 

Effects. — Bland  or  aseptic  emboli  produce  chiefly  mechanical  effects 
referable  to  the  obstruction  to  the  circulation;  toxic  or  septic  emboli  cause 
also  other  changes  which  may  be  described  as  chemical  or  infective.  We 
shall  consider  first  the  mechanical  effects. 

The  direct  injury  which  may  be  inflicted  upon  the  vessel  wall  by  sharp 
calcareous  emboli  is,  according  to  Ponfick,  a  rare  cause  of  aneurysm. 
Embolic  aneurysms,  however,  stand  in  much  more  definite  relation  to 
chemical  properties  of  the  embolus,  as  will  be  shown  subsequently  (p.  218). 

Necrosis;  Infarction. — The  fate  of  a  part  supplied  by  an  artery  closed 
by  a  bland  embolus  depends  altogether  upon  whether  it  is  fed  within  a 
certain  time  after  the  obstruction  with  enough  arterial  blood  to  presence 
its  function  and  integrity.  An  embolus  which  does  not  completely  plug 
the  vessel  may  cause  no  appreciable  interference  with  the  circulation;  but 
the  closure  of  the  lumen  is  usually  soon  effected  by  a  secondary  thrombus. 
The  occlusion  by  a  bland  embolus  of  an  artery  with  al)undant  anastomoses, 
such  as  those  possessed  by  the  arteries  supplying  bone,  the  voluntary 
muscles,  the  skin,  the  thyroid,  the  uterus,  usually  causes  no  circulatory  dis- 
turbance of  any  consequence.  Even  in  these  situations  extensive  multiple 
embolism,  or  embolism  with  extensive  secondary  thrombosis,  may  cause 
local  anaemia  with  its  consequences. 

Sudden  death  may  be  the  result  of  embolism  of  the  trunk  or  a  main 
division  of  the  pulmonary  artery,  of  one  of  the  coronary  arteries  of  the 
heart,  or  of  the  bulbar  arteries. 
16 


203  EMBOLISM 

If  an  adequate  collateral  circulation  be  not  established  within  the  proper 
time  the  inevitable  fate  of  a  part,  supplied  by  an  embolised  artery,  is  degen- 
eration or  death.  Local  death  is  the  regular  reisult  of  enibolism  of  branches 
of  the  splenic  artery,  the  renal  artery,  the  basal  arteries  of  the  brain, 
the  central  artery  of  the  retina,  and  the  main  trunk  of  the  superior  mesen- 
teric arterv.  It  is  the  usual  result  of  embolism  of  one  of  the  coronary 
arteries  of  the  heart,  if  the  patient  survive  long  enough;  and  it  is  the 
inconstant  result,  depending  generally  upon  accessory  circumstances,  of 
embolism  of  the  medium-sized  and  smaller  branches  of  the  pulmonary 
arteries,  of  cerebral  arteries  other  than  the  basal,  of  the  abdominal  aorta, 
iliacs,  main  arteries  of  the  extremities,  and  some  other  arteries.  A  col- 
lateral circulation  may  be  established  sufficiently  to  preserve  the  life  of 
a  part,  but  not  to  maintain  its  full  nutrition  ;  under  these  circumstances  it 
undergoes  fatty  degeneration  or  simple  atrophy. 

When  the  dead  part  is  so  surrounded  with  living  tissue  that  it  can  be 
permeated  witli  ]ym]ih,  as  is  usually  the  case  in  the  viscera,  the  mode  of 
death  is  that  described  by  Weigert,  and  named  by  Cohnheim  "•  coagu- 
lative  necrosis."  Here  the  dead  protoplasm,  and  to  some  extent  inter- 
cellular substances,  undergo  chemical  changes,  believed  to  be  in  pairt 
coagulative;  and  actual  fibrillated  fibrin  may  appear.  If  there  be  enough 
coagulable  material  present,  the  necrotic  part  becomes  hard,  dry,  opaque, 
and  somewhat  swollen.  For  a  time  its  general  architecture,  both  gross 
and  microscopic,  is  preserved;  but  the  nuclei  and  specific  granulations 
disappear  early,  the  former  largely  by  karyorrhexis. 

An  area  of  coagulative  necrosis  resulting  from  shutting  off  of  the 
blood-supply  is  an  infarct.  Its  shape  corresponds  to  that  of  the  arterial 
tree  supplying  it,  and  is,  therefore,  as  a  rule,  approximately  conical,  or 
that  of  a  wedge,  the  base  being  toward  the  periphery  of  the  organ.  The 
wedge-shape  is  most  marked  in  smaller  infarcts;  large  ones  may  be  round- 
ish or  irregular  in  shape.  The  si/.e  depends  upon  that  of  the  occluded 
artery.  The  colour  is  opaque,  white,  or  yellowish,  unless  haemorrhage  is 
added  to  the  necrosis.  We  thus  distinguish  ana-mic,  pale  or  white  infarcts, 
and  red  or  ha'morrhagic  infarcts;  but,  in  the  latter  no  less  than  in  the 
former,  the  essential  thing  is  the  coagulative  necrosis,  tlie  ha'morrhage 
being  merely  something  added  to  the  necrosis.  This  was  not  always  clearly 
recognised,  it  being  sui)i)osed  at  one  time  that  the  hjemorrliage  was  the  char- 
acteristic feature  of  infarcts,  and  tliat  })ale  infarcts  were  simply  decolour- 
ised ha'morrhagic  infarcts.  The  name  "  infarcts  "  (from  infarcire,  to  stuff), 
like  many  other  old  medical  terms,  is  therefore  now  used  in  a  sense  at 
variance  witii  its  etymological  meaning.  In  some  situations,  as  the  kidney 
and  tiie  retina,  the  infarct  is  nearly  always  pale;  in  others,  as  the  lungs  and 


EMBOLISM  203 

the  intestine,  it  is  as  constantly  hEemorrhagic ;  and  in  yet  others,  as  the  spleen 
and  the  heart,  it  may  be  eitiier  white  or  red. 

Where  there  is  not  a  sufficient  quantity  of  coagnlable  substances  the 
area  of  coagulative  necrosis  does  not  become  hard;  and  it  may  be  of 
much  softer  consistence  than  normal,  as  is  the  case  with  the  ischaeraic 
necroses  of  the  brain  and  spinal  cord.  Necrosis  of  peripheral  parts,  as 
the  toes,  foot,  leg,  hand,  is  not  of  the  coagulative  variety;  for  the  dead 
part  is  not  surrounded  by  living  tissue  to  furnish  the  lymph  which  brings 
one  of  the  factors  essential  for  coagulation.  This  peripheral  necrosis  is 
called  gangrene  or  mortification,  and  may  be  either  dry  or  moist. 

Collateral  Circulation;  Local  Anccmia. — As  the  state  of  the  collateral 
circulation  is  the  decisive  factor  in  bland  embolism,  it  becomes  important 
to  learn  the  conditions  under  which  establishment  or  failure  of  this  cir- 
culation occurs.  This  subject  is  one  eminently  open  to  experimental 
study ;  but  more  attention  has  been  given  to  the  anatomical  than  to  the 
physiological  side.  In  fact  many  writers  seem  to  assume  that  the  physi- 
ological factors  can  be  so  readily  deduced  from  the  laws  of  hydro-dynamics 
that  it  is  only  necessary  to  investigate  the  size,  arrangement,  and  distribu- 
tion of  the  vascular  tubes.  Nevertheless  experience  has  shown  abundantly 
the  danger  of  accepting  anything  in  the  physics  of  the  circulation  which  has 
not  been  put  to  an  experimental  test  on  the  living  body.  The  experimental 
study  of  the  physiological  conditions  wliich  determine  the  development  of 
a  collateral  circulation  has  demonstrated  that  this  problem  is  by  no  means 
so  simple  as  has  been  often  represented ;  while  some  old  errors  have  been 
corrected  and  new  facts  have  been  added,  we  are  still  far  from  an  entirely 
satisfactory  solution  or  any  definite  agreement  of  opinion.  It  is  impos- 
sible here  to  do  more  than  touch  upon  certain  points  bearing  directly 
upon  the  subject  in  hand. 

If  an  artery  with  slender  anastomoses  to  its  area  of  distribution,  sucli 
as  the  femoral  or  the  ligual  in  a  frogs  tongue,  be  tied,  the  immediate 
effect  is  stoppage  of  the  circulation  and  anaemia  of  the  part  supplied  by  the 
occluded  vessel,  accompanied  by  contraction  of  the  artery  below  the  obstruc- 
tion. Almost  immediately,  or  within  a  short  time,  the  blood  begins  to  flow 
with  greatly  increased  velocity  through  arteries  arising  above  the  point 
of  ligation,  but  more  rapidly  only  through  those  which  send  blood  by 
anastomosing  channels  to  the  anemic  part.  At  the  same  time  these 
arteries  with  quickened  flow  dilate.  Formerly  this  vascular  dilatation 
and  increased  flow  were  attributed  to  rise  of  blood-pressure  above  the  liga- 
ture, but  experiments  have  shown  that  in  most  situations  this  is  a  factor  of 
relatively  little  moment.  The  rise  of  pressure  cannot  of  course  remain 
localised,  and  after  ligation  of  the  femoral  artery   amounts  at  most  to 


204  EMBOLISM 

only  a  few  millimetres  of  mercury.  Evidence  of  the  relatively  slight 
importance  of  this  increased  pressure  is  that  the  ligated  artery  actually 
contracts  from  the  point  of  ligation  to  the  first  branch  arising  above  the 
ligature  (Thoma,  Goldenblum)  ;  and  that  the  phenomena  of  dilatation  and 
increased  velocity  occur  only  in  arteries  which  send  blood  to  the  anaemic 
area,  although  others  which  carry  blood  elsewhere  may  arise  nearer  to  the 
point  of  obstruction  (Xothnagel).  Moreover,  it  is  hardly  conceivable 
that  increased  pressure  above  the  ligature  can  persist  for  the  days  and 
weeks  which  may  be  necessary  for  the  full  development  of  the  collateral 
circulation. 

As  the  increased  flow  cannot  be  due  to  any  change  in  the  viscosity  of 
the  blood,  it  must  be  due  to  increase  of  the  pressure  gradient.  Therefore, 
if  it  is  not  the  result  in  any  marked  degree  of  rise  of  pressure  alwve  the 
obstruction,  it  must  be  caused  by  lowered  resistance  to  the  stream  in  the 
anastomosing  vessels.  A  moment's  reflection  will  show  that  this  is  2  far 
more  purposeful  and  better  mode  of  compensation  than  one  brought  abat 
exclusively  by  a  rise  of  pressure  which  must  act  upon  arteries  in  no  way 
concerned  in  the  collateral  circulation.  The  difficulty  is  an  entirely  satis- 
factory and  complete  explanation  of  the  lowered  resistance.  It  seems 
impossible  that  it  can  be  due  to  anything  but  a  widening  of  the  bed  of  the 
stream.  Yon  Recklinghausen  has  ]X)inted  out  that  the  stream-bed  for  the 
anastomosing  arteries  is  enlarged,  inasmuch  as  after  occulsion  of  the  main 
artery  the  blood  can  flow  from  these  collaterals  not  only  in  its  original  bed, 
but,  also,  with  diminished  resistance,  into  the  stream-bed  belonging  to  tlie 
closed  artery.  The  pressure  gradient  is  thus  increased,  and  consequently 
the  velocity  of  the  current  is  quickened  in  the  anastomosing  arteries.  The 
cause  of  the  dilatation  of  these  arteries  is  not  so  clear.  Thoma  states  as  his 
first  histo-mechanical  principle  that  increased  velocity  of  the  blood-current 
leads  to  widening  of  the  lumen,  and  eventually,  if  the  increase  continues, 
to  growth  of  the  vessel  wall  in  superficies.  Admitting  this  to  be  true,  it 
can  hardly  be  considered  an  explanation.  As  the  collateral  circulation 
develops  perfectly,  and  with  the  same  phenomena,  after  severance  of  all 
connection  of  the  part  with  the  central  nervous  system,  it  is  evident  that 
vaso-motor  influences  which  are  under  central  control  are  not  essential 
to  the  process. 

Satisfactory  as  von  Recklinghausen's  explanation  is,  as  far  as  it  goes, 
there  is  evidence  that  it  does  not  cover  all  of  the  facts,  and  that  there  is 
also  some  mechanism  by  which  the  vessels  of  an  isihivmic  part  are  opened 
wide  for  the  re<'ej)tion  of  the  needed  arterial  blood.  The  existence  of 
such  a  mechanism  has  been  recognised  by  Lister,  Cohniieim,  Bier,  and 
others.     I  must  refer  especially  to  the   recent  papers  of  Bier  for  a  full 


EMBOLISM  205 

presentation  of  the  evidence  on  this  point,  and  shall  merely  mention,  as 
a  familiar  illustration,  the  extreme  arterial  hypersemia  which  follows  the 
removal  of  an  Esmarch  bandage.  This  flushing  of  a  previously  ischa}mic 
part  with  arterial  blood  has  been  usually  attributed  to  paralysis  of  vaso- 
constrictor or  stimulation  of  vaso-dilator  nerves,  but  Bier  has  shown  that 
it  occurs  under  conditions  where  this  explanation  can  be  probably  excluded. 

Without  following  Bier  in  his  somewhat  vitalistic  conceptions,  or  specu- 
lating regarding  the  explanation  of  the  phenomenon,  we  must,  I  think, 
admit  that  deprivation  of  arterial  blood  sets  up  some  condition  of  a  part 
whereby  the  vessels  Avhich  feed  it  are  in  some  way  dilated  to  receive  any  fresh 
arterial  blood  which  can  reach  them.  The  existence  of  such  an  admirably 
adaptive,  self-regulatory  capacity  must  be  an  important  element  in  the  de- 
velopment of  a  collateral  circulation,  and  it  may  be  remarked  that  it  is  a 
physiological  rather  than  an  anatomical  factor.  Bier  believes  that  tliis 
capacity  is  very  unequally  developed  in  different  parts  of  the  body;  being 
highest  in  external  parts,  and  feeble  or  absent  in  most  of  the  viscera.  He 
is  also  of  the  opinion  that  the  arterioles  and  capillaries  of  external  parts  have 
the  power,  by  independent  contractions,  of  driving  blood  into  the  veins ;  and 
that,  by  contraction  of  the  small  veins  the  capillaries  of  these  parts  are  in 
large  measure  protected  from  the  reception  of  venous  blood. 

A  possible,  but  I  think  not  fully  demonstrated,  variation  in  the  power  to 
lower  the  resistance  to  the  collateral  stream  of  arterial  blood  is  not,  however, 
the  only  physiological  property  which  influences  the  varying  effects  following 
obstruction  to  the  arterial  supply  of  different  parts  of  the  body.  In  some 
situations  there  are  physiological  arrangements  which  seem  calculated  to 
increase  the  difficulty  of  establishing  an  adequate  collateral  circulation, 
ilall  has  shown  that  contraction  of  the  intestine  exerts  a  marked  influence 
upon  the  circulation  through  this  organ.  In  the  light  of  his  results,  it  is 
interesting  to  note  that,  immediately  after  closure  of  the  main  trunk  of  the 
superior  mesenteric  artery  of  a  dog,  the  intestine  is  thrown  into  violent  tonic 
contractions  and  remains  in  an  anaemic,  contracted  condition  for  two  or  three 
hours;  after  which  the  spasm  relaxes  and  the  bloodless  condition  at  once 
gives  place  to  venous  hyperaemia  and  hivmorrhagic  infarction,  which  appears 
in  the  third  to  sixth  hour  after  the  occlusion  of  the  artery  (Mall  and  Welch). 
This  intestinal  contraction,  which  under  these  circumstances  is  equivalent  to 
arterial  spasm,  is  probably  one,  although  not  the  sole,  reason  why,  in  spite 
of  free  anastomoses,  occlusion  of  the  arteries  supplying  the  intestine  is  fol- 
lowed by  necrosis  and  haemorrhage.  That  the  explanation  is  not  to  be  found 
simply  in  the  great  length  of  intestine  supplied  by  a  single  arterv',  is  evident 
from  the  fact  that,  if  the  extra-intestinal  arteries  supplying  a  loop  much 
more  than  5  centimetres  in  length  be  suddenly  closed,  the  loop  becomes 


206  EMBOLISM 

hnemorrhajTic  and  necrotic  (Mall  and  Welch,  Bier).  That  the  conditions  are 
essentially  identical  in  man  is  proven  by  the  experience  of  surgeons,  who  have 
repeatedly  observed  the  same  results  after  separation  of  the  mesentery  close 
to  tlie  intestine  over  about  the  same  length.  The  blood  can  enter  at  each 
end  of  the  short  loop  arteries,  whose  branches  anastomose  freely  within  the 
walls  of  the  loop  with  those  of  the  closed  arteries ;  there  being  a  particularly 
rich  arterial  plexus  in  the  submucous  coat  (Heller).  But  these  anastomoses 
are  insufficient  to  preserve  the  part;  although,  with  reference  to  the  extent 
of  territory  to  be  supplied,  they  are  large  in  comparison  with  some  of  the 
trivial  anastomoses  which  in  external  parts  can  respond  effectively  to  the 
call  for  a  collateral  circulation  to  far  larger  areas.  It  must  be  left  to  future 
investigations  to  determine  how  far  the  inability  of  the  intestinal  vessels 
to  compensate  circulatory  obstructions  of  a  degree  readily  compensated  in 
many  other  situations  may  be  due,  as  claimed  by  Bier,  to  an  inherent  inca- 
pacity to  lessen  the  resistance  to  tlie  collateral  stream,  or  to  contraction  of  the 
muscular  coats  of  the  intestine,  or  to  other  causes.  As  Panski  and  Thoma 
have  shown  that  slowing  and  interruption  of  the  circulation  in  the  spleen  is 
followed,  for  several  hours,  by  contraction  of  the  muscular  trabecular,  it  is 
probable  that  the  development  of  a  collateral  circulation  in  this  organ  meets 
an  obstacle  similar  to  that  in  the  intestine. 

The  various  organs  and  tissues  differ  so  widely  as  regards  their  suscepti- 
bility to  the  injurious  effects  of  lack  of  arterial  blood  that  local  anaemia  of 
equal  intensity  and  duration  may  in  one  part  of  the  body  produce  no  appre- 
ciable effect,  and  in  another  cause  the  immediate  abolition  of  function  and 
the  inevitable  death  of  the  part.  In  general,  the  more  highly  differentiated, 
specific  cells  of  an  organ  are  those  which  suffer  first  and  most  intensely.  At 
one  end  of  the  scale  are  the  ganglion  cells  of  the  brain,  which,  after  the 
withdrawal  of  arterial  blood  for  iialf  an  liour,  and  j)rol)ably  for  a  much 
shorter  time,  cannot  1)C  restored  to  life;  and  at  the  other  end  may  be  placed 
the  periosteum,  the  cells  of  which  may  be  still  capable  of  producing  bone 
two  or  three  days  after  all  circulation  has  ceased.  So  susceptible  to  local 
anaemia  are  the  ganglion  cells  of  the  central  nervous  system,  that  not  only  is 
emi)olism  of  the  l)ranches  of  the  cerebral  arteries  with  only  capillary  com- 
munications, even  of  the  minute  terminal  twigs  in  the  cortex,  always  followed 
by  necrotic  softening,  but  also  embolism  of  the  anastomosing  arteries  in  the 
pia  very  often  causes  softening  of  at  least  a  part  of  the  area  supplied  by  the 
plugged  artery.  In  the  well-known  Stenson  experiment,  temporary  closure 
of  the  rabbit's  abdominal  aorta,  just  below  the  origin  of  the  renal  arteries, 
for  an  hour,  results  in  the  inevital)le  death  of  the  ganglion  cells  in  the  central 
gray  matter  of  the  lunihar  cord;  and  this  notwithstanding  the  free  anas- 
tomoses of  thi'  anterior  and  posterior  spinal  arteries.     Many  of  the  lesions 


EMBOLISM  207 

which  pass  under  the  names  of  myelitis  and  ha?morrhagic  encephalitis  pre- 
sent the  histological  characters  of  ischaemic  necrosis,  although  often  no 
arterial  occlusion  can  be  found. 

Perhaps,  next  to  elements  of  the  nervous  system,  the  epithelial  cells  of 
the  cortical  tubules  of  the  kidney  are  most  susceptible  to  ischaemia.  Litten 
has  demonstrated  that  the  temporary  ligation  of  the  renal  artery  of  the 
rabbit  for  one  and  a  half  to  two  hours  is  followed  invariably  by  necrosis  of 
many  of  these  epithelial  cells.  The  cells  in  the  walls  of  the  blood-vessels  and 
of  connective  tissue  are  relatively  insusceptible  to  temporary'  slowing  or 
cessation  of  the  circulation. 

It  is  evident  from  the  preceding  statements  that  the  nature  of  the  organ 
or  tissue  has  a  very  important  influence  in  determining  whether  local 
necrosis  follows  arterial  embolism. 

I  have  dwelt  in  some  detail,  although  within  the  limited  space  necessarily 
inadequately,  upon  certain  physiological  characters  of  the  circulation  and 
of  different  organs  and  tissues,  which  appear  to  me  deserving  of  more  con- 
sideration than  is  usually  given  to  them  in  discussions  of  the  causes  of 
embolic  necroses  and  infarctions.  It  is,  of  course,  not  to  be  inferred  that 
the  number  and  size  of  the  anastomoses  are  not  of  prime  importance  in  de- 
termining the  mechanical  effects  of  arterial  embolism,  but,  important  as 
they  are,  they  are  not  the  exclusive  determinants  of  the  result.  There  is  no 
single  anatomical  formula  applicable  to  the  circulatory  conditions  under 
which  all  embolic  infarcts  occur.  The  nearest  approach  to  such  a  formula  is 
that  embodied  in  Cohnlieim's  doctrine  of  terminal  arteries,  a  name  which 
he  gave  to  arteries  whose  branches  do  not  communicate  with  each  other  or 
with  those  of  other  arteries,  although  capillaries  are  of  course  everywhere  in 
communication  with  each  other.  Terminal  vessels  in  this  sense  are  the  renal, 
the  splenic,  the  pulmonary,  the  central  artery  of  the  retina,  the  basal  arteries 
of  the  brain,  and  in  general  all  branches  of  cerebral  and  spinal  arteries  after 
they  have  penetrated  the  brain  or  the  spinal  cord,  the  intramuscular  branches 
of  the  coronary  arteries  of  the  heart,  and  the  portal  vein.'  Cohnheim's 
teaching  was  that  infarction  occurs  always  after  embolism  of  a  terminal 

'  There  is  some  confusion  as  to  the  sense  in  which  the  words  "  terminal  arter- 
ies "  should  be  used,  and  it  must  be  admitted  that  later  investigations  have  de- 
tracted from  the  precision  given  to  this  term  by  Cohnheim.  Thus  some  do  not 
recognise  the  pulmonary  artery  as  terminal,  because  the  lung  is  supplied  likewise 
by  the  bronchial  and  several  other  arteries  whose  capillaries  communicate  with 
those  of  the  pulmonary  artery.  But  unless  we  make  the  extent  of  a  second 
arterial  supply  the  decisive  point  in  the  definition,  we  should  have,  for  the  same 
reason,  to  exclude  the  renal  and  the  splenic  arteries  from  the  class  of  "  terminal 
arteries."  Then  the  conception  of  arteries  which  are  "  functionally  "  but  not 
automatically  terminal,  creates  still  further  confusion. 


208  EMBOLISM 

vessel,  except  of  the  pulmonary  artery,  whose  capillaries,  under  ordinary 
conditions,  arc  numerous  and  wide  enough,  after  obliteration  of  an  arterial 
branch,  to  maintain  a  sufficient  circulation;  and  of  the  portal  vein  whose 
capillaries  communicate  freely  with  those  of  the  hepatic  artery.  Thoma  and 
Goldenblum  have  sliown  that,  contrary  to  Cohnheim's  results,  no  infarction 
follows  embolism  or  ligature  of  the  frog's  lingual  artery,  which  is  or  can 
readily  be  made  a  terminal  artery,  provided  the  tongue  be  replaced  in  the 
mouth  after  the  operation  so  as  to  avoid  stretching  and  drying  from  exposure 
to  the  air.  It  is,  therefore,  quite  possible  in  some  situations  for  an  adequate 
circulation  to  be  carried  on  through  merely  capillary  communications,  al- 
though the  conditions  are  of  course  less  favourable  than  when  there  are 
arterial  anastomoses.  On  the  other  hand,  as  we  have  seen,  embolism  of 
anastomosing  arteries,  such  as  the  mesenteric  and  the  cerebral,  may  be  fol- 
lowed by  necrosis  or  infarction ;  and  it  cannot  be  sa.id  tliat  the  anastomoses 
in  all  of  these  cases  are  so  unimportant  that  the  arteries  are  virtually  terminal. 

We  may  conclude  then  that,  under  ordinary  conditions,  embolism  of  an 
artery  having  abundant  and  large  anastomoses  has  no  important  mechanical 
effect;  that  embolism  of  an  artery  with  few  and  minute  anastomoses, 
especially  emijolism  of  an  artery  with  only  capillary  communications,  is  in 
many  situations  followed  by  necrosis,  this  result  being  favoured  by  certain 
physiological  conditions  which  have  been  considered;  and  that  embolism 
of  arteries  with  fairly  well-developed  anastomoses  may  in  certain  situations 
also  cause  necrosis.  Among  the  factors  iniiuencmg  the  result,  other  than 
those  relating  to  the  number  and  size  of  the  anastomoses,  are  the  varying 
susceptibility  of  cells  to  ischa?mia,  interference  with  the  circulation  by  con- 
traction of  muscular  constituents  of  a  part,  and  perhaps  some  inherent  weak- 
ness in  the  physiological  part  of  the  mechanism  by  which  a  vigorous  collateral 
circulation  is  established. 

The  compensation  of  sudden  occlusion  of  an  artery,  by  means  of  the 
collateral  circulation,  generally  presupposes  vessels  with  fairly  nonnal  walls 
and  a  certain  vigour  of  the  circulation.  When  the  arteries  have  lost  their 
elasticity,  or  the  general  circulation  is  feeble,  or  there  is  some  pre-existing 
obstacle  to  the  circulation  such  as  chronic  passive  congestion,  the  develop- 
ment of  an  adequate  collateral  circulation  is  rendered  correspondingly 
difficult,  and  may  be  impossible.  Hence  embolism  of  arteries  of  the  extremi- 
ties is  often  followed  by  gangrene  in  the  aged,  in  arterio-sclerosis,  in  heart 
disease,  and  in  infective,  anaemic,  and  exhausting  diseases.  There  are  some 
obsers'ations  which  suggest  that  arterial  spasm  may  co-operate  with  embolism 
in  causing  local  anaemia. 

The  agencies  by  which  a  sufficient  collateral  circulation  is  established  may 
be  Uirown  out  of  order  to  such  a  degree  that  embolism  of  arteries  having 


EMBOLISM  209 

even  the  most  ample  anastomoses  may  be  followed  by  necrosis.  Foci  of  cere- 
bral softening  have  been  observed  after  occlusion  of  the  internal  carotid  or 
of  one  of  the  vertebral  arteries ;  although  the  circle  of  Willis,  the  largest  and 
most  perfect  anastomosis  in  the  body,  was  open,  and  no  vascular  obstruction 
could  be  found  beyond  it.  Here,  doubtless,  an  important  factor  in  this  ex- 
^eptional  occurrence  is  the  rapidity  with  which  nerve  cells  die  when  insuffi- 
ciently fed  with  arterial  blood.  Cohn  narrates  the  interesting  case  of  a 
young  woman  rendered  extremely  anamic  by  repeated  hsemorrhages  from 
cancer  of  the  tongue.  In  order  to  control  the  bleeding  the  right  carotid 
was  tied.  The  patient  immediately,  to  all  appearances,  lost  consciousness; 
acquired  ptosis  of  the  right,  then  of  the  left  eye,  drawing  of  the  angle  of  the 
mouth  to  the  right,  and  relaxation  and  almost  complete  paralysis  of  the  left 
extremities.  The  pulse  almost  disappeared  and  the  face  became  very 
anasmic.  Eespiration  was  unaffected.  The  ligature  was  at  once  removed, 
and  at  the  same  moment  the  patient  awoke  "  as  from  a  dream,"  and  the 
symptoms  just  mentioned  quickly  disappeared.  She  said  that  she  had  not 
completely  lost  consciousness  but  was  unable  to  speak,  and  that  her  will 
had  lost  control  over  the  organs.  She  had  lost  so  much  blood  that  she  died 
three  hours  later  without  again  losing  consciousness  before  death.  At  the 
autopsy  the  carotids  and  all  of  the  cerebral  vessels  were  found  open,  and 
there  was  no  change  in  the  brain  except  ansemia.  In  this  case,  the  general 
anagmia  was  evidently  so  great  that  after  closure  of  one  carotid,  wliicli 
probably  lasted  not  more  than  a  minute  or  two,  a  sufficient  supply  of  blood 
could  not  reach  the  brain  through  the  circle  of  Willis. 

Hcemorrhagic  Infarction. — The  explanation  of  the  accumulation  and 
extravasation  of  blood  in  haemorrhagic  infarcts  has  been  the  subject  of 
much  speculation  and  experimental  study.  It  is  only  in  certain  situa- 
tions that  infarcts  are  hemorrhagic  throughout;  and,  as  already  mentioned, 
these  are  no  less  necrotic  than  are  the  white  infarcts.  The  necrosis  and 
the  hemorrhage  are  co-ordinate  effects  of  the  disturbance  of  the  circula- 
tion, neither  being  caused  by  the  other.  Yirchow,  in  his  early  writings, 
suggested  as  possibilities,  without  definitely  adopting  any  of  tbem,  most 
of  the  explanations  which  have  since  been  advanced  to  account  for  the 
apparently  paradoxical  phenomenon  that  the  occlusion  of  an  artery  may 
be  followed  by  hyperemia  and  hemorrhage  in  the  area  of  its  distribu- 
tion. Cohnheim,  on  the  basis  of  experimental  investigations  published 
in  1872,  came  to  the  conclusion  that  the  hyperaemia  which  may  follow 
arterial  embolism  is  the  result  of  regurgitant  flow  from  the  veins,  that 
the  hemorrhage  occurs  by  diapedesis,  and  that  this  diapedesis  is  the 
result  of  some  molecular  change  in  the  vascular  walls  deprived  of  their 
normal  supply  of  nutriment.     Although   Cohn,  in  1860,  had  shown  con- 


210  EMBOLISM 

clusively,  by  numerous  experiments  on  various  orirans,  that  the  hypcrgemia 
and  ha^morriiage  are  not  the  result  of  regurgitant  flow  from  tlie  veins, 
Cohnheim's  views  were  widely  accepted  until  Litten,  in  1880,  in  apparent 
ignorance  of  Cohn's  work,  repeated  the  experiments  of  the  latter  upon 
this  point  with  the  same  results.  The  experiments  of  Dr.  Mall  and  myself 
upon  luvmorrhagic  infarction  of  the  intestine  in  1887  convinced  us  that 
the  blood  which  causes  the  infarct  is  not  regurgitated  from  veins.  Cohn- 
heim's results  upon  the  frog  as  to  the  source  of  tlie  blood  in  infarcts  have 
not  been  confirmed  by  subsequent  experimenters  (Zielonko,  Kossuchin, 
Kiittner,  Goldenblum,  Thoma). 

In  situations  where  closure  of  an  artery  is  followed  by  lupmorrhagic 
infarction,  tying  the  veins  also,  so  as  to  shut  off  all  opportunity  for  reflux 
of  venous  blood,  increases  the  hyperaemia  and  the  htemorrhage;  and  it 
may  render  an  infarct  hcnemorrhagic  which  otherwise  be  anaemic.  On  the 
other  hand,  if  all  vascular  communication  of  a  part  be  cut  off  except  that 
with  the  veins,  the  part  undergoes  simple  necrosis  without  hannorrliagic 
infarction;  and  the  result  is  the  same  even  if  the  artery  be  cut  open,  so 
as  to  afford  apparently  the  most  favoural)le  opportunity  for  backward  flow 
from  the  veins.  Or,  expressed  differently,  if  after  closure  of  an  artery 
all  possibility  of  access  of  blood  to  the  obstructed  area  through  anastomos- 
ing arteries  and  capillaries  be  prevented,  the  veins  remaining  open,  the 
part  dies  without  hamiorrhagic  infarction.  Cohnheim  was  in  error  in 
supposing  that  luiemorrhagic  infarction  cannot  occur  where  the  veins  arc 
])rovided  with  valves,  for  it  has  been  shown  by  Bryant,  Koppe,  and  ]\Iall 
that  the  small  intestinal  veins  of  the  dog  have  effective  valves ;  yet  nowhere 
can  ha^morrhagic  infarction  be  more  readily  produced  experimentally  by 
arterial  obstruction  than  in  the  intestine  of  this  animal.  It  is,  then,  quite 
certain  that  the  blood  which  accunmlates  in  the  capillaries  and  small  veins, 
and  is  extravasated  in  hamorrhagic  infarction,  comes  in  through  the 
capillary,  and,  if  they  exist,  the  arterial  anastomoses,  and  is  not  regurgitated 
from  tlie  veins. 

It  cjuinot  be  doubted  that  the  red  corpuscles  escape  by  dia|)edesis,  not  by 
rhexis;  but  our  experiments  are  in  entire  accord  with  those  of  Litten 
in  failing  to  furnish  any  support  to  the  prevalent  doctrine  that  the  hemor- 
rhage is  the  result  of  ciianges  in  the  walls  of  the  vessels  caused  by  insuf- 
ficient supply  of  arterial  blood ;  in  fact  they  seem  to  us  more  conclusive 
upon  this  point.  If  a  loop  of  intestine  be  completely  shut  off  from  the 
circulation  for  tiiree  or  four  hours  (by  which  time,  after  ligation  of  the 
superior  mesenteric  artery,  ha^morrhagic  infarction  begins  to  appear),  and 
the  obstruction   be  then  removed,   the   blood   at  once  shoots   in   from   tiic 


EMBOLISM  211 

arteries  with  great  rapidity,  and  distends  the  vessels.'  If,  as  usually 
happens,  the  blood  has  not  coagulated  in  the  vessels,  no  haemorrhagic  infarc- 
tion subsequently  appears.  If,  immediately  after  the  circulation  has  been 
fully  re-established  in  the  loop,  the  superior  mesenteric  artery  be  ligated, 
the  intestine  from  the  lower  part  of  the  duodenum  into  the  colon  becomes 
the  seat  of  haemorrhagic  infarction  in  the  usual  time ;  but  the  infarction 
does  not  appear  earlier  and  is  not  more  intense  in  the  part  which  Rad  been 
previously  deprived  of  its  circulation  for  three  or  four  hours  than  in  the 
rest  of  the  small  intestine.  It  is  true,  as  Cohnheim  has  shown,  that  re-estab- 
lishment of  a  local  circulation,  after  its  stoppage  for  many  hours  or  days, 
may  be  followed  by  haemorrhages  in  the  previously  ischaemic  area ;  but 
haemorrhagic  infarction  after  arterial  occlusion  begins  long  before  it  is 
possible  to  demonstrate  this  change  in  the  vascular  wall  caused  by  lack  of 
blood-supply. 

In  a  part  undergoing  haemorrhagic  infarction  the  circulation  is  greatly 
retarded  in  consequence  of  the  small  difference  between  the  arterial  and 
the  venous  pressures.  This  result  may  be  brought  about  by  rise  of  the 
venous  or  lowering  of  the  arterial  pressure.  If  the  veins  are  obstructed 
sufficiently  to  render  the  outflow  nil,  or  very  small,  and  the  arteries  are 
open,  the  infarction  is  intense,  and  occurs  with  high  intracapillary  pressure. 
In  consequence  of  the  free  anastomoses  of  veins  this  mode  of  production 
of  an  infarct  is  rare,  but  it  may  occur  after  thrombosis  of  the  mesenteric, 
the  splenic,  and  the  central  retinal  veins.  Its  explanation  offers  no  especial 
difficulties.  If  the  veins  are  open  the  arterial  pressure  must  be  reduced 
in  order  to  furnish  the  conditions  necessar}'  for  the  production  of  ha?mor- 
rhagic  infarction.  This  later  cases  is  the  one  present  in  arterial  embolism 
with  haemorrhagic  infarction,  and  is  the  one  especially  needing  explana- 
tion. The  intracapillary  pressure  in  this  case  may  vary,  but  will  generally 
be  low.  The  arterial  pressure  is  so  low  that  the  lateral  pulse-waves  nearly 
or  entirely  disappear,  so  that  the  force  which  drives  the  blood  into  the 
capillaries  is  no  longer  the  normal  intermittent  one,  which  experiment 
has  shown  to  be  essential  for  the  long-continued  circulation  of  the  blood 
through  the  capillaries  and  veins.  This  reduction,  or  absence  of  lateral 
pulsation,  to  which,  so  far  as  I  know,  other  experimenters  have  not  called 
attention,  I  believe  to  be  the  factor  of  first  importance  in  the  causation  of 
haemorrhagic  infarction  following  arterial  embolism. 

We  are  not  sufficiently  informed  concerning  the  physical  and  vital 
properties  of  the  blood  and  of  the  blood-vessels  to  be  able  to  predict  posi- 

*  Bier's  experimental  results  concerning  the  absence  of  hyperaemia  after  tem- 
porary ischaemia  of  the  intestine  do  not,  according  to  our  experience,  apply  to 
prolonged  ischaemia,  which  we  found  to  be  followed  by  intense  hyperaemia. 


212  EMBOLISM 

lively  what  would  happen  under  such  abnormal  circulatory  conditions 
as  those  named,  and  actual  observation  only  can  furnish  a  solution.  The 
difficulties  in  making  such  observations  under  the  requisite  conditions  are 
considerable.  Dr.  Mall  and  I,  in  examining  microscopically,  in  a  specially 
constructed  apparatus,  the  mesenteric  circulation  of  the  dog  after  liga- 
gation  of  the  superior  mesenteric  artery,  observed  that  immediately  after 
the  occlusion  the  circulation  ceases  in  the  arteries,  capillaries,  and  veins. 
In  a  short  time  the  circulation  returns,  but  with  altered  characters.  The 
arteries  are  contracted,  but  may  subsequently  dilate  somewhat;  and  the 
blood  from  the  collaterals  flows  through  them  with  diminished  rapidity, 
and  without  distinct  lateral  pulsation.  The  direction  of  the  current  is 
reversed  in  some  of  the  arteries.  The  movement  of  the  blood  in  the  capil- 
laries and  veins  is  sluggish  and  irregular.  The  direction  of  the  current 
in  some  of  the  veins  may  be  temporarily  reversed,  but  we  were  unable 
to  trace  a  regurgitant  venous  flow  into  the  capillaries.  The  distinction 
between  axial  and  plasmatic  current  is  obliterated.  Gradually  the  smaller 
and  then  the  larger  veins  become  more  and  more  distended  with  red 
corpuscles,  and  all  of  the  phenomena  of  an  intense  venous  hyperaemia 
appear,  so  that  one  instinctively  searches  for  some  obstruction  to  the 
venous  outflow.  The  red  corpuscles  in  the  veins  tend  to  accumulate  in 
clumps,  and  may  be  moved  forward,  or  forward  and  backward,  in  clumps 
or  solid  columns.  Stasis  appears  in  the  veins.  This  is  at  first  observed 
only  here  and  there  and  is  readily  broken  up  by  an  advancing  column  of 
blood ;  but  it  gradually  involves  more  and  more  of  the  veins,  and  in  some 
becomes  permanent,  producing  an  evident  obstacle  to  the  forward  move- 
ment of  the  blood.  Tlie  same  phenomena  of  distention  with  red  corpuscles, 
clumping,  to-and-fro  movement,  and  stasis  appear  gradually  in  the  capil- 
laries. An  interesting  appearance,  sometimes  observed  in  capillaries  and 
veins,  is  that  of  interrupted  columns  of  compacted  red  corpuscles  with 
intervening  clear  spaces  which  are  sometimes  clumps  of  white  corpuscles, 
sometimes  of  platelets,  sometimes  only  clear  plasma.  With  the  partial 
blocking  of  the  veins  and  capillaries,  red  corpuscles  begin  to  pass  through 
the  walls  of  these  vessels  by  diapedesis;  and  after  a  time  the  haemorrhage 
becomes  so  great  that  it  is  difficult  to  observe  the  condition  within  the 
vessels.  The  venous  outflow  is  diminished  immediately  or  shortly  after 
the  closure  of  the  superior  mesenteric  artery;  it  then  rises,  but  later  it 
continuously  falls  to  a  niiniinuni. 

An  experiment  wliich  we  made  shows  that  the  blood  for  hjemorrhagic 
infarction  need  not  necessarily  enter  from  the  collaterals,  and  it  sheds 
some  light  u]H)n  tlie  condition  of  the  circulation  during  the  production 
of  the   infarct.     We   ligatcd   all    of   the   vascular  communications    of  the 


EMBOLISM  213 

intestine,  with  the  exception  of  the  main  artery  and  vein,  and  then  tied 
the  intestine  above  and  below,  so  that  the  included  intestine  was  supplied 
only  by  the  main  artery  and  the  blood  returned  by  the  main  vein.  Under 
these  circumstances  no  infarction  results.  We  then  by  a  special  device 
gradually  constricted  the  main  arter}'.  In  repeated  experiments  we  found 
that  not  until  the  artery  is  sufficienty  compressed  to  stop  the  lateral  pul- 
sations in  its  branches — the  pressure  in  the^a  being  then  about  one-fifth 
of  the  normal — does  hsemorrhagic  infarction  appear.  Precautions  were 
taken  to  make  sure  that  tlie  flow  through  the  constricted  main  artery  and 
its  branches  continued,  and  that  the  vein  remained  open.  We  have  often 
measured  the  blood-pressure  in  branches  of  the  superior  mesenteric  artery 
after  ligation  of  this  artery  and  during  the  progress  of  an  infarction,  and 
have  found  it  to  be  generally  one-fourth  to  one-fifth  of  the  normal  pressure. 
If  the  pressure  on  the  arterial  side  falls  below  a  certain  minimum  no 
haemorrhage  occurs  in  the  infarction. 

It  is  evident  from  the  preceding  description  that  the  phenomena  observed 
under  these  peculiar  circulatory  conditions  are  in  large  part  dependent 
upon  the  physical  properties  of  the  blood,  especially  upon  its  viscosity 
and  the  presence  of  suspended  particles  which  readily  stick  together;  and 
differ  in  important  respects  from  those  which  would  occur  under  similar 
conditions  with  a  thin,  homogeneous  fluid.  The  pressure  gradient  from 
arteries  to  veins  of  the  ischsemic  area  is  so  low  that  the  red  corpuscles 
cannot  fully  overcome  the  resistance  in  the  veins  and  capillaries.  They 
accumulate  in  these  situations,  and  probably  undergo  some  physical  change 
by  which  they  become  adherent  to  each  other  and  to  the  vascular  wall. 
The  absence  of  the  normal  pulse-waves  prevents  the  breaking  up  of  these 
masses  of  corpuscles,  the  longitudinal  pulse-waves  sometimes  obsers'ed 
having  little  or  no  effect  in  disintegrating  the  masses.  In  this  way  numer- 
ous small  veins  and  capillaries  become  blocked,  with  a  resulting  rise  of 
intracapillary  pressure  and  diminution  of  outflow  of  blood  through  the 
veins.  Von  Frey  has  shown  by  interesting  experiments  that  an  intermit- 
tent pulsating  force  is  necessary  to  prevent  the  speedy  blocking  of  veins  and 
capillaries  with  red  corpuscles  in  carrying  on  artificial  circulation  with 
defibrinated  blood  througli  living  organs.  Kronecker  has  also  demonstrated 
the  influence  of  a  pulsating  force  in  increasing  the  venous  outflow. 

The  diapedesis  is  due  to  the  slowing  and  stagnation  of  the  blood,  and  to 
the  blood-pressure.  Without  a  certain  height  of  pressure  there  is  no 
diapedesis;  and,  with  a  given  retardation  and  stasis  of  the  blood-current, 
the  higher  the  intracapillary  and  intravenous  pressure  the  greater  the 
amount  of  diapedesis.  The  matter  which  needs  explanation  is  that  the 
diapedesis  may  occur  with  lower  than  the  normal  pressure,  and  through 


214  EMBOLISM 

vessel  walls  apparently  unaltered.  This  I  attribute  to  the  fact  that  the 
red  corpuscles,  in  consequence  of  the  slow  circulation,  have  opportunity 
to  become  engaged  in  the  narrow  paths  followed  by  the  lymph  as  it  passes 
out  between  the  endothelial  cells.  Diapedesis  is  a  slow  process,  and  the 
channels  for  it  are  much  smaller  than  the  thickness  of  a  red  corpuscle. 
Unless  the  red  corpuscles  can  get  started  on  the  path  between  the  endo- 
thelial cells,  they  cannot  traverse  it;  and  unless  the  circulation  is  very 
much  slowed,  and  the  outer  plasmatic  current  obliterated,  there  is  no 
opportunity  for  the  corpuscles  to  become  engaged  between  the  endothelial 
cells,  provided,  that  is,  the  vascular  wall  be  normal.  With  greatly  retarded 
circulation  there  is  opportunity,  and  when  the  way  in  front  is  blocked  by 
compact  masses  of  red  corpuscles,  and  sometimes  by  actual  thrombi,  the 
only  path  open  to  the  corpuscles  is  that  followed  by  the  lymph  between 
the  endothelial  cells.  This  then  becomes  the  direction  of  least  resistance 
for  their  movement. 

The  reason  why  infarctions  are  haemorrhagic  in  some  situations  and 
not  in  others  offers  difficulties  chiefly  in  consequence  of  our  ignorance 
of  the  exact  circulatory  conditions  which  lead  to  the  production  of  infarc- 
tion in  different  parts  of  the  body.  It  is  generally  assumed  that  these 
circulatory  conditions  are  everywhere  essentially  the  same;  but  this  is 
by  no  means  proven.  As  we  have  already  seen,  the  physiological  conditions 
which  influence  the  result  are  various.  It  may  be,  therefore,  that  the 
requisite  intracapillary  and  intravenous  pressure,  or  some  other  condition 
of  the  circulation  essential  for  the  production  of  hemorrhagic  infarction, 
is  lacking  when  the  infarction  is  anaemic.  In  general  a  high  venous  pres- 
sure favours  hajmorrhage  in  an  infarction,  and  a  low  arterial  pressure 
opposes  it.  The  pressure  in  the  superior  mesenteric  and  portal  veins  is 
higher  than  in  any  other  veins  of  the  body.  Ha3morrhagic  infarction  of 
the  lung  occurs  especially  with  high  degrees  of  chronic  passive  congestion 
in  which  the  venous  pressure  is  elevated.  Thrombosis  of  veins  seems  to 
l)e  the  cause  of  at  least  some  of  the  haimorrhagic  infarcts  of  the  spleen. 
H.Tmorrliagic  infarction  of  the  kidney  may  be  produced  experimentally 
by  ligating  the  renal  veins. 

The  studies  of  recent  years  uiion  the  formation  lymph  have  demonstrated 
that  the  blood-vessels  in  different  regions  differ  markedly  in  their  perme- 
ability, those  of  the  intestine  being  probably  the  most  permeable.  It  may 
be  that  this  difference  in  the  constitution  of  the  vessels  is  an  imi)ortant 
factor  in  determining  the  extent  of  diapedesis  under  similar  circulatory 
conditions.  As  pointed  out  by  Weigert,  however,  the  greatest  influence 
appears  to  be  exercised  by  the  resistance  offered  by  the  tissues  to  the 
escape  of  red  corpuscles  from  tlie  vessels.     Ihvmorrhagic  infarction  occurs 


EMBOLISM  215 

especially  where  this  tissue-resistance  is  low,  as  in  the  loose,  spongy  tex- 
ture of  the  lungs,  and  in  the  soft  mucosa  and  lax  submucosa  of  the  intestine. 
The  haemorrhage  is  far  less  in  the  dense  muscular  coats  of  the  intestine. 
The  considerable  resistance  offered  by  the  naturally  firm  consistence  of 
the  kidney  is  increased  by  the  swelling  and  hardness  resulting  from  coagu- 
lative  necrosis  of  the  epithelial  and  other  cells  of  this  organ;  so  that 
infarcts  in  this  situation  are  nearly  always  anaemic  in  the  greater  part 
of  their  extent,  although  often  haemorrhagic  in  the  periphery.  The  spleen 
is  of  softer  consistence  tlian  the  kidney;- and  here  both  white  and  red 
infarcts  may  occur,  the  latter  especially  with  increased  venous  pressure. 
Although  infarcts  of  the  brain  are  soft,  they  are  much  swollen  in  the 
fresh  state  from  infiltration  with  serum,  so  as  to  displace  surrounding 
parts  (Marchand).  Here  also  there  must  be  considerable  resistance  to 
the  passage  of  red  corpuscles  through  the  vascular  walls;  but  it  is  not 
uncommon  for  these  softened  areas  to  present  scattered  foci  of  haemorrhage, 
and  -sometimes  they  are  markedly  ha?morrhagic.  The  intraocular  pressure 
is  probably  a  factor  in  making  embolic  infarcts  of  the  retina  anaemic. 
Embolism  of  arteries  of  the  extremities  with  insufficient  collateral  circu- 
lation is  often  associated  with  extravasations  of  blood  in  the  ischaemic  areas. 
Metamorphoses  of  Infarcts. — A  bland  infarct  is  a  foreign  body  most 
of  the  constituents  of  which  are  capable  of  absorption  and  replacement 
by  connective  tissue.  The  red  corpuscles  lose  their  colouring  matter,  some 
of  which  is  transformed  into  amorphous  or  crystalline  haematoidin.  Poly- 
nuclear  leucocytes,  through  chemiotactic  influences,  wander  in  from  the 
periphery,  the  advance  guard  being  usually  the  seat  of  marked  nuclear 
fragmentation.  This  nuclear  detritus  mingles  with  that  derived  from 
the  dead  cells  of  the  part.  Granulation  tissue  develops  from  the  living 
tissue  around  the  infarct.  Young  mesoblastic  cells  wander  in  and  assist 
the  leucocytes  in  their  phagocytic  work.  In  the  course  of  time  the  debris, 
which  becomes  extensively  fatty,  is  disintegrated  and  removed ;  new  vessels 
and  new  connective  tissue  grow  in;  and  finally  a  scar,  more  or  less  pig- 
mented according  to  the  previous  content  of  blood,  marks  the  site  of  the 
infarct.  In  chronic  endocarditis,  depressed,  wedge-shaped  scars  are  often 
found  in  the  spleen  and  the  kidneys.  They  are  rare  in  the  lungs,  not 
because  haemorrhagic  infarcts  in  this  situation  usually  undergo  resolu- 
tion like  pneumonia  or  simple  htemorrahges,  but  because  pulmonary  infarcts 
generally  occur  under  conditions  not  compatible  with  the  prolonged  sur- 
vival of  the  patient.  Partly  organised  infarcts  are  not  uncommon  in  the 
lungs.  In  the  brain,  ischaemic  softening  may  remain  for  a  long  time  with 
apparently  little  change;  but  the  common  ultimate  result  is  a  cyst-like 
structure,  which  may  be  more  or  less  pigmented,  and  is  characterised  *by 


216  EMBOLISM 

a  meshwork  of  delicate  neuroglia  and  connective-tissue  fibres,  infiltrated 
with  milky  or  clear  serum.  Into  the  finer  histological  details  of  the  pro- 
cess of  substitution  of  an  infarct  by  scar-tissue  it  is  not  necessary  here 
to  enter. 

Chemical  Effects.  Metastases. — Embolism  and  metastasis  are  some- 
times employed  as  practically  synonymous  terms;  but,  in  ordinary  usage, 
by  metastasis  is  understood  any  local,  morbid  condition  produced  by  the 
transportation  of  pathological  material  by  the  lymphatic  or  blood-current 
from  one  part  of  the  body  to  another. 

We  have  already  considered  the  coarser  bland  emboli  in  respect  of  their 
mechanical  effects.  Similar  emboli,  so  small  as  to  become  lodged  only  in 
arterioles  or  capillaries,  produce  no  mechanical  effects  unless,  as  rarely 
happens,  numerous  arterioles  or  capillaries  are  obstructed.  The  subject  of 
transportation  of  pigment  granules,  and  that  of  metallic  and  carboniferous 
dust,  producing  the  various  konioses,  does  not  fall  within  the  scope  of  this 
article.  On  account  of  certain  special  features,  emboli  of  air,  of  fat,  and  of 
parenchyma-cells  are  most  conveniently  considered  separately  (pp.  222-228). 
There  remain,  in  contrast  to  the  dead  and  inert  emboli  to  which  our  atten- 
tion has  been  especidly  directed,  those  containing  tumour-cells  and  para^sitic 
organisms,  or  their  products. 

^Masses  of  tumour  growing  into  a  blood-vessel  may  be  broken  off  and 
transported  as  course  emboli,  producing  all  of  the  mechanical  effects  which 
we  have  described.  There  have  been  instances  of  sudden  death  from  block- 
ing of  the  pulmonary  artery  by  cancerous  or  sarcomatous  emboli,  as  in  a  case 
reported  by  Feltz.  It  is,  however,  as  a  cause  of  metastatic  gro\\i;hs  that 
emboli  of  tumour-cells  have  their  chief  significance.  In  individual  cases  it 
is  oftener  a  matter  of  faith  than  of  demonstration  that  the  metastasis  is  due 
to  such  emboli,  for  opportunities  to  bring  absolutely  conclusive  proof  of  this 
mode  of  origin  of  secondary  tumours  are  not  common.  There  have,  however, 
been  enough  instances  in  which  the  demonstration  has  been  rigorous  to 
establish  firmly  the  doctrine  of  the  embolic  origin  of  metastatic  tumours. 
The  evidence  is  that  tumour-metastases  are  far  more  frequently  due  to 
capillar}'  emboli  than  to  tliose  of  larger  size.  Cancers  and  sarcomas  furnish 
the  great  majority  of  eml)oli  of  this  class;  but  in  rare  instances  even  benign 
tumours  may  penetrate  blood-vessels  and  give  rise  to  emboli,  which  excepv- 
tionally  are  the  starting-points  of  secondary  growths  of  the  same  nature  as 
the  primary.  Mention  has  already  been  made  of  paradoxical  and  retrograde 
transport  of  tumour-emlK)li,  as  well  as  of  the  possibility  of  emboli  of  tumour- 
cells  being  so  small  as  to  traverse  the  pulmonary  capillaries. 

Certain  animal  parasites,  as  Filaria  sanguinis,  Bilharzia  hcematohia, 
and  Pla.smodiu.Tn  malarice,  are  inhabitants  of  the  blood,  or,  in  certain  stages 


EMBOLISM  217 

of  their  existence  within  the  human  body,  are  frequently  found  there. 
According  to  observations  of  Cerfontaine  and  Askanazy,  the  usual  mode  of 
transportation  from  the  intestine  of  the  embryos  of  trichina  is  by  the  lym- 
phatic and  blood-currents.  Echinococci  have  been  known  to  pass  from  the 
liver  through  the  vena  cava;  or  primarily  from  the  right  heart  into  the 
pulmonary  artery;  and  emboli  from  echinococci  present  in  the  wall  of  the 
left  heart  may  be  transported  to  distant  organs  (Davaine).  Amoeba  coli 
has  been  found  in  the  intestinal  veins;  and,  as  stated  by  Dr.  Lafleur  in 
his  article  on  "Amoebic  Abscess  of  the  Liver"  (Allbutt's  "System  of 
Medicine,"  V,  p.  156),  it  is  probable  that  this  parasite  can  reach  the  liver 
tiirough  the  portal  vein. 

On  account  of  their  frequency  and  serious  consequences,  infective  emboli 
containing  pathogenetic  bacteria  are  of  especial  significance.  Such  emboli 
constitute  an  important  means  of  distribution  of  infective  agents  from  pri- 
mary foci  of  infection  to  distant  parts  of  the  body,  where  the  pathogenetic 
micro-organisms,  by  their  multiplication  and  their  chemical  products,  can 
continue  to  manifest  their  specific  activities.  These  emljoli  are  often  derived 
from  infective  venous  thrombi  connected  with  some  primary  area  of  infec- 
tion. The  portal  of  infection  may  be  through  the  integument,  the  alimentary 
canal,  the  respiratory  tract,  the  genito-urinary  passages,  the  middle  ear,  or 
the  eye,  with  corresponding  infective  thrombo-phlebitis  in  these  various 
situations.  Or  there  may  be  no  demonstrable  atrium  of  infection,  as  in  many 
cases  of  infective  endocarditis,  which  constitutes  an  important  source  of  in- 
fective emboli.  Emboli  may  of  course  come  from  secondary  and  subsequent 
foci  of  infection. 

Coarse  emboli  are  by  no  means  essential  for  the  causation  of  infective 
metastases,  nor  is  it  necessary  that  there  should  be  any  thrombosis  to  afford 
opportunity  for  the  distribution  of  micro-organisms  from  a  primary  focus. 
Bacteria  may  gain  access  to  the  circulation,  singly  or  in  clumps;  and  such 
bacteria,  without  being  enclosed  in  plugs  of  even  capillary  size,  may  become 
attached  to  the  walls  of  capillaries  and  small  vessels  and  produce  local  metas- 
tases. In  tliis  way  infective  material  coming  from  the  systemic  veins  may 
pass  through  the  pulmonary  capillaries  without  damage  to  the  lungs,  and 
become  localised  in  various  organs  of  the  body. 

We  cannot  explain  the  various  localisations  of  infective  processes  in  in- 
ternal organs  of  the  body  exclusively  by  the  mechanical  distribution  of 
pathogenetic  micro-organisms  by  the  circulation.  We  must  reckon  with  the 
vital  resistance  of  the  tissues,  which  varies  in  different  parts  of  the  body,  in 
different  species  and  individuals,  and  with  reference  to  different  organisms. 
Even  the  pyogenetic  micrococci,  which  are  capable  of  causing  abscesses  any- 
where in  the  body,  do  not  generally  produce  their  pathogenetic  effects  in 
17 


218  EMBOLISM 

every  place  wliere  they  may  chance  to  lodge.  They  have  their  seats  of  prefer- 
ence, which  vary  in  diiferent  species  of  auimal  and  probably  in  different 
individuals. 

The  mere  presence  of  pathogenetic  bacteria  in  an  embolus  does  not  neces- 
sarily impart  to  it  infective  properties.  This  is  true  even  of  emboli  contain- 
ing pyogenetic  cocci.  I  have  in  several  instances  observed  in  the  spleen  and 
kidney  only  the  mechanical,  bland  effects  of  emboli  derived  from  the  vegeta- 
tions of  acute  infective  endocarditis,  and  have  been  able  to  demonstrate 
streptococci  or  other  pathogenetic  organisms  in  the  original  vegetations  and 
in  the  emboli.  As  lias  already  been  remarked  concerning  thrombi,  the  line 
cannot  be  sharply  drawn  between  bland  emboli  and  septic  emboli,  simply  on 
the  basis  of  the  presence  of  bacteria  ;  although  of  course  the  septic  properties 
must  be  derived  from  micro-organisms. 

Infective  emboli  are  capable  of  producing  all  of  the  mechanical  effects 
of  bland  emboli ;  to  these  are  added  the  specific  effects  of  the  micro-organisms 
or  their  products.  These  latter  effects  are  essentially  chemical  in  nature, 
and  may  occur  wherever  the  emboli  lodge,  being  thus  independent  of  tlie 
particular  circulatory  conditions  essential  for  the  production  of  mechanical 
effects.  The  most  iniportaut  of  these  chemical  effects  are  haemorrhages, 
usually  of  small  size,  and  of  an  entirely  different  causation  from  those  of 
hemorrhagic  infarction;  necroses;  inflammation,  often  suppurative,  and, 
in  case  of  putrefactive  bacteria,  gangrenous  putrefaction.  The  most  im- 
portant funetion  of  infective  embolism  is  in  tlie  causation  of  pyeemia.  This 
subject  has  been  most  competently  presented  by  Professor  Cheyne  in  All- 
butt's  "  System  of  Medicine,"  I,  p.  601,  who  has  left  nothing  which  requires 
further  consideration  here. 

Embolic  Aneurysms. — Both  the  first  recognition  and  the  correct  explana- 
tion of  emlx)lic  aneurysms,  at  least  of  the  great  majority  of  cases,  belong  to 
British  physicians  and  surgeons.  Tufnell,  in  18o3,  called  attention  to  the 
influence  of  emboli  in  causing  aneurysmal  dilatation.  There  followed  ob- 
servations by  Ogle,  Wilkes,  Holmes,  Church,  and  E.  W.  Smith,  before  the 
appearance,  in  1873,  of  Ponfick's  important  paper  on  embolic  aneurysms. 
Ponfick  explained  their  formation  by  direct  injury  to  the  vessel-wall,  inflicted 
usually  by  calcareous,  spinous  emboli ;  a  view  which  has  since  been  confirmed 
only  by  Tboma.  In  1877,  Goodhart,  in  reporting  a  case  gave  the  first 
satisfactory  explanation  of  the  mode  of  production  of  most  of  these  aneu- 
rysms. He  pointed  out  their  association  with  acute  infective  endocarditis, 
and  referred  them  to  acute  softening  of  the  arterial  wall,  caused  by  toxic 
emboli.  Other  observations  followed;  and  in  1885  Osier  reported  a  case 
wliich,  although  not  embolic,  belongs  etiologically  to  the  same  general  cate- 
gory.    Tliis  was  a  case  of  multiple  myiotic  aneurysms  of  the  aorta  due  to 


EMBOLISM  219 

infective  endaortitis  associated  with  infective  endocarditis.  In  1886  and 
1887  appeared  the  contributions  of  Langton  and  Bowlby,  the  most  valuable 
in  English  literature,  who  fully  confirmed  and  expanded  in  detail  the  views 
first  briefly  amiounced  by  Goodhart.  Eppinger,  in  his  extensive  monograph 
on  aneurysms  published  in  1887,  presented  the  results  of  a  minute  and  care- 
ful study  of  this  class  of  aneurysm,  which  he  calls  aneurysma  mycotico- 
embolicum,  and  reported  seven  personal  observations.  Of  later  papers  on 
the  subject  may  be  mentioned  those  of  Pol  and  Spronck,  Duckworth,  Buday, 
and  Clarke. 

The  evidence  is  conclusive  that  aneur}'sms  may  be  caused  by  the  destruc- 
tive action  of  bacteria  contained  in  emboli  or  directly  implanted  on  the  inner 
vascular  wall.  The  usual  source  for  such  emboli  in  relation  to  aneurysm 
is  furnished  by  acute  infective  endocarditis;  but  as  there  is  every  transition 
from  ordinary  warty  endocarditis  to  the  most  malignant  forms,  and  as  the 
same  species  of  micro-organisms  may  be  found  in  the  relatively  benign  as 
in  the  maligiiant  cases,  no  single  type  of  endocarditis  is  exclusively  associated 
with  these  aneurysms.  As  is  demonstrated  by  Osier's  case,  the  same  result 
may  follow  a  mycotic  endarteritis  not  secondary  to  em})olism. 

Eppinger  has  shown  that  at  least  the  intima  and  the  internal  elastic 
lamella,  and  usually  a  part,  sometimes  the  whole,  of  the  media,  are  destroyed 
by  the  action  of  the  bacteria,  when  an  aneurj^sm  is  produced.  The  site  of 
the  aneurysm  coiTCsponds  to  this  circumscribed  area  of  destruction,  and 
therefore  to  the  seat  of  the  embolus,  and  is  not  above  it,  as  some  have  sup- 
posed. The  aneurysm  is  usually  formed  acutely,  sometimes  slowly.  It  may 
remain  small  or  attain  a  large  size.  Multiplicity  and  location  at  or  just 
above  an  arterial  branching  are  common  characteristics  of  embolic  aneurysms. 
Favorite  situations  are  the  cerebral  and  mesenteric  arteries  and  arteries  of 
the  extremities;  but  these  aneurysms  may  occur  in  almost  any  artery. 
Arteries  without  firm  support  from  the  surrounding  tissues  offer  the  most 
favourable  conditions  for  the  production  of  embolic  aneurysms. 

Eppinger  totally  rejects  direct  mechanical  injury  from  an  embolus  as  a 
cause  of  aneurysm  in  the  manner  alleged  by  Ponfick ;  and  Langton  and 
Bowlby  are  likewise  sceptical  as  to  the  validity  of  Ponfick's  explanation  be- 
yond its  possible  application  to  some  of  his  own  cases.  Certainly  the  great 
majority  of  embolic  aneurysms  are  caused  by  pathogenetic  organisms,  and 
belong,  therefore,  to  the  class  of  parasitic  aneurysms  rather  than  to  that  of 
traumatic  aneurysms.    The  affection  is  not  a  common  one. 

In  this  connection  mere  mention  may  be  made  of  the  interesting  and  very 
common  verminous  aneurysms  of  the  anterior  mesenteric  artery  of  horses, 
caused  by  Strongylus  armatus. 

Geneeal  Symptoms. — The  symptoms  of  bland  embolism  are  dependent 
mainly  upon  the  degree  and  extent  ol  the  local  anaemia  produced  by  the 


220  EMBOLISM 

arterial  obstruction,  and  upon  the  specific  functions  of  the  part  involved.  In 
infective  embolism  there  are  additional  symptoms  referable  to  local  and 
general  infection.  Here  the  constitutional  symptoms  usually  overshadow 
those  referable  to  the  embolic  obstruction  and  the  local  lesions. 

It  is  not  known  that  any  symptoms  attend  the  act  of  transportation  of 
an  embolus,  even  through  the  heart.  In  some  situation  there  is  sudden  pain 
at  the  moment  of  impaction  of  the  embolus  (embolic  ictus).  This  is  more 
marked  in  large  arteries,  especially  those  supplying  the  extremities,  than  in 
smaller  and  visceral  arteries.  This  pain  has  been  attributed  to  various 
causes;  but  the  most  probable  explanation  seems  to  me  to  be  irritation,  by 
the  impact  of  the  embolus  and  by  the  sudden  distension  of  the  artery,  of 
sensory  nerves  and  nerve-endings  in  the  vascular  wall,  present  especially  in 
the  outer  coat.  It  may  ]>e  that  the  Pacinian  corpuscles,  which  are  particu- 
larly abundant  in  and  around  the  adventitia  of  the  abdominal  aorta,  the 
mesenteric  arteries,  the  iliac  and  the  femoral  arteries,  are  susceptible  to 
painful  impressions.  Embolism  of  the  arteries  named  is  characterised 
especially  by  the  intensity  of  the  pain,  described  sometimes  as  the  sensation 
of  a  painful  blow,  at  the  moment  of  impaction  of  the  embolus.  Surgeons 
are  familiar  with  the  pain  which  attends  the  act  of  ligation  of  larger  blood- 
vessels. 

Of  the  pain  which  follows  arterial  embolism  there  are  other  causes, 
such  as  irritation  of  sensory  nerves  by  local  anaemia,  altered  tension  of 
the  part,  presence  of  waste  and  abnormal  metabolic  products,  structural 
changes  in  nerves,  inflammation  of  serous  membranes  covering  infarcts, 
and  so  forth. 

Some  writers  have  spoken  of  the  occasional  occurence  of  a  nervous  or 
reflex  chill  at  the  time  of  the  embolic  act;  but,  without  denying  the  pos- 
sibility of  such  an  occurrence,  I  think  that  chills  associated  with  embolism 
have  been  due  usually  to  infection  rather  than  to  vascular  plugging. 

Although  Strieker  has  constructed  a  hypothesis  of  fever  based  largely 
up)on  experiments  interpreted  by  him  as  demonstrating  that  the  commo- 
tion mechanically  set  up  by  emboli  causes  fever,  I  am  not  aware  of  any 
conclusive  obsen'ations  which  show  that  fever  may  be  produced  in  this 
way  in  human  beings.  Independently  of  the  intervention  of  pathogenetic 
micro-organisms,  arterial  embolism  may,  however,  be  accompanied  by  ele- 
vation of  temperature.  Direct  invasion  of  thermic  nervous  centres  is,  of 
course,  only  a  special  case  in  certain  localisations  of  cerebral  embolism. 
Gangolphe  and  Courmont  attribute  the  fever  sometimes  observed  after 
arterial  occlusion  to  the  absorption  of  pyretogenetic  substances  which  they 
find  produced  in  tissues  undergoing  necrobiosis.  Other  possible  causes 
of  fever  may  be  the  reactive  and  secondary  inflammations  consecutive  to 
embolism. 


EMBOLISM  221 

Only  in  external  parts,  or  parts  open  to  inspection,  can  the  phenomena 
of  mortification,  or  "  local  cadaverisation,"  as  Cruveilhier  designated  the 
results  of  shutting  off  arterial  blood,  be  directly  observed.  Here  are  mani- 
fest the  pallor  accompanied  by  patches  of  lividity,  the  cessation  of  pul- 
sation, the  loss  of  turgidity,  the  coldness,  the  annihilation  of  function, 
the  local  death.  The  hfemorxhages  which  result  from  arterial  obstruction 
may,  however,  be  evident,  not  in  external  parts  only,  but  also  by  the  dis- 
charge of  blood  from  the  respiratory  passages,  the  intestine,  and  the  urinary 
tract;  as  the  result  of  pulmonary,  intestinal,  and  renal  infarction  respec- 
tively. The  phenomena  following  retinal  embolism  are  open  to  direct 
inspection  by  the  ophthalmoscope.  In  parts  not  accessible  to  physical 
exploration  the  symptoms  are  referable  mainly  to  the  disturbance  or  aboli- 
tion of  function,  and,  therefore,  vary  with  the  special  functions  of  the 
part.  They  will  be  considered  in  connection  with  embolism  of  special 
arteries  (p.  229). 

Diagnosis. — The  main  reliance  in  the  differential  diagnosis  of  embolism 
from  thrombosis,  or  from  other  forms  of  arterial  obstruction,  is  the  dis- 
covery of  a  source  for  emboli,  the  sudden  onset  and  the  intensity  of  symp- 
toms referable  to  local  arterial  anaemia,  occasionally  the  disappearance  or 
marked  improvement  of  symptoms  in  consequence  of  complete  or  partial 
re-establishment  of  the  circulation,  and  to  some  extent  the  absence  of 
arterio-sclerosis  or  other  causes  of  primary  arterial  thrombosis. 

Valuable  as  these  characters  are  for  diagnosis,  they  are  neither  always 
present  nor  infallible.  For  pulmonary  embolism  the  source  is  to  be  sought 
in  peripheral  venous  thrombosis  or  cardiac  disease  with  thrombi  in  the 
right  heart;  for  embolism  in  the  aortic  system,  the  usual  source  is  the  left 
heart,  the  great  majority  of  cases  being  associated  with  disease  of  the 
aortic  or  mitral  valves.  It  may,  however,  be  impossible  to  detect  the 
source,  and  its  existence  does  not  exclude  the  occurrence  of  thrombosis  or 
other  forms  of  arterial  occlusion. 

Nor  are  the  symptoms  consecutive  to  embolism  always  sudden  in  onset. 
An  embolus  may  at  first  only  partly  obstruct  the  lumen  of  the  vessel,  which 
is  later  closed  by  a  secondary  thrombus;  or  it  may  be  so  situated  that  a 
thrombus  springing  from  it  is  the  real  cause  of  the  local  anaemia.  For 
example,  an  embolus  lodged  in  the  internal  carotid  arterj'  usually  causes 
no  definite  symptoms,  but  a  secondary  thrombus  may  extend  from  the 
embolus  into  the  middle  cerebral  artery,  in  which  case  cerebral  softening 
is  sure  to  follow.  On  the  other  hand,  the  complete  closure  of  an  artery 
may  be  effected  by  a  thrombus  with  such  rapidity  as  to  suggest  embolism. 

Wliile  the  sudden  occlusion  of  an  artery  by  an  embolus  often  causes 
temporary  ischasmia  of  greater  intensity  and  over  a  larger  area  than  the 


222  EMBOLISM 

more  gradual  clo.-iure  of  the  same  artery  by  a  thrombus,  so  tliat  when  the 
collateral  circulation  is  fully  established  the  disappearance  or  reduction 
of  the  symptoms  may  be  more  marked  in  the  former  case  than  the  latter, 
there  may  be  even  in  thrombosis  very  decided  improvement  in  the  symp- 
toms with  the  development  of  the  collateral  circulation. 

The  existence  of  arterio-sclerosis,  of  course,  does  not  exclude  embolism; 
but  in  case  of  doubt  the  chances  are  strongly  in  favour  of  embolism  in 
children  and  young  adults  vv'ith  healthy  arteries,  especially  if  cardiac  dis- 
ease be  present;  the  most  common  association  in  the  latter  cases  being  with 
mitral  affections. 

Xotwithstanding  all  of  these  uncertainties,  the  diagnosis,  of  embolism, 
when  it  produces  definite  symptoms,  can  be  correctly  made  in  the  majority 
of  cases. 

Air  Embolism. — The  majority  of  cases  in  which  deatli  has  been  attri- 
buted to  the  entrance  of  air  into  the  circulation  have  been  surgical  opera- 
tions and  wounds  al)out  the  neck,  .shoulder,  upper  part  of  the  thorax  and 
skull,  where  air  has  been  sucked  into  gapping  veins  and  sinuses  by  thoracic 
aspiration;  and  cases  in  which  air  has  entered  the  uterine  veins,  chiefly 
from  the  puerperal  uterus,  either  spontaneously,  as  after  alwrtions  or 
detachment  of  placenta  previa,  or  after  injections  into  the  uterine  cavity. 
Jiirgensen  has  reported  cases  in  which  he  believes  death  was  caused  by  the 
entrance  of  gas  into  open  veins  connected  with  diseased  areas  in  the  stomach 
and  intestine,  (.iaseous  embolism  has  been  assigned  as  the  cause  of  symp- 
toms and  of  death  in  caisson-disease  and  in  divers ;  and  it  has  been  observed 
in  connection  with  the  development  of  gas-producing  bacilli  in  the  body. 
A  large  number  of  experiments  have  been  made  to  determine  the  effects 
of  air  introduced  into  the  circulation.  These  have  demonstrated  that  when 
the  air  is  introduced  slowly  and  at  intervals,  enormous  quantities  can  some- 
times be  injected  in  a  comparatively  short  time  without  manifest  injury. 
Thus  Laborde  and  Muron  injected  into  the  external  jugular  vein  of  a  dog 
1120  cc.  in  the  space  of  an  hour  and  a  half  without  causing  death;  and 
Jiirgensen  injected  into  the  left  femoral  artery  of  a  dog,  weighing  43.5  kilo, 
3550  cc.  in  the  space  of  two  hours  and  a  lialf  with  only  slight  disturbance 
of  the  respiration  and  of  the  action  of  the  heart.  Under  these  circumstances 
the  air-bubbles  circulate  with  the  blood,  pass  through  the  capillaries,  and 
are  speedily  eliminated.  Small  amounts  of  air  introduced  directly  into 
the  carotids,  the  left  heart  or  thoracic  aorta,  are  often  quickly  fatil  from 
embolism  of  the  cerebral  or  coronary  arteri&s. 

The  sudden  introduction  of  large  amounts  of  air  into  the  veins  is  quickly 
fatal.  Kabbits  are  much  more  susceptible  to  air  embolism  than  dogs  or 
horses.     50  cc.  of  air,  ami  even  more,  can  often   be  injected  at  once  into 


EMBOLISM  233 

the  external  jugular  vein  of  a  medium-sized  dog  without  causing  death; 
nor  can  a  dog  \ye  killed  by  simple  aspiration  of  air  into  the  veins,  even 
when  an  open  glass  tube  is  inserted  into  the  axillary  or  jugular  vein  and 
shoved  into  the  thorax  (Feltz).  Barthelemy  says  that  as  much  as  4000  cc. 
of  air  must  he  introduced  into  the  veins  of  horses  in  order  to  cause  death. 

After  death  from  entrance  of  air  into  the  veins,  the  right  cavities  of 
the  heart  are  found  distended  with  frothy  blood,  and  blood  containing  air- 
bubbles  is  found  in  the  veins — especially  those  near  the  heart,  and  in  the 
pulmonary  artery  and  its  branches.  It  .is  exceptional  under  these  cir- 
cumstances for  air  to  pass  through  the  pulmonary  capillaries  into  the 
left  heart  and  aortic  system. 

There  are  two  principal  explanations  of  the  cause  of  death  in  these  cases. 
According  to  one,  associated  especially  with  Couty's  name,  the  air  is 
churned  up  with  the  blood  into  a  frothy  fluid  in  the  right  heart,  and  on 
account  of  its  compressibility  this  mixture  cannot  be  propelled  by  the 
right  ventricle,  which  thus  becomes  over-distended  and  paralysed.  Ac- 
'  cording  to  another  hypothesis,  supported  by  experiments  of  Passet  and  of 
Hauer,  blood  mixed  with  air-bubbles  is  propelled  into  the  pulmonary  artery 
and  its  branches,  but  the  frothy  mixture  cannot  be  driven  through  the  pul- 
monary capillaries,  so  that  death  results  from  pulmonary  embolism.  The 
paralysing  influence  upon  the  heart  of  obstruction  to  the  coronary  circula- 
tion from  accumulation  of  air  in  the  right  heart  and  in  the  coronary  veins 
must  also  be  an  important  factor,  as  well  as  the  cerebral  ana?mia.  Prob- 
ably all  of  these  factors — over-distension  of  the  right  heart,  embolism  of 
the  pulmonary  arteiT  and  its  branches  and  of  the  coronary  veins,  and  cere- 
bral angemia — may  be  concerned  in  causing  death,  although  not  necessarily 
all  in  equal  degree  in  every  case. 

We  have  no  information  as  to  the  amount  of  air  required  to  cause  death 
by  intravenous  aspiration  or  injection  in  human  beings.  It  seems  certain 
that  man  is  relatively  more  susceptible  in  this  respect  than  the  dog  or 
the  horse;  but  it  is  probable  that  the  fatal  quantity  of  air  must  be  at  least 
several  cubic  centimeters,  and  that  the  entrance  of  a  few  bubbles  of  air 
into  the  veins  is  of  no  consequence.  Many  authors  have  entertained  very 
exaggerated  ideas  of  the  danger  of  entrance  of  a  small  quantity  of  air 
into  the  veins. 

A  large  proportion  of  the  cases  reported  in  medical  records  as  deaths 
due  to  air  embolism  will  not  stand  rigid  criticism.  1  have  had  occasion  to 
look  through  the  records  of  a  large  number  of  these  eases,  and  have  been 
amazed  at  the  frequently  unsatisfactory  and  meagre  character  of  the  evidence 
upon  which  was  based  the  assumption  that  death  was  due  to  the  entrance 
of  air  into  the  circulation. 


224  EMBOLISM 

So  far  as  I  am  aware,  the  first  attempt  to  make  a  bacteriological  exami- 
nation and  to  determine  the  nature  of  the  gas-bubbles  found  in  the  blood 
under  circumstances  suggestive  of  death  from  entrance  of  air  into  the  vessels, 
was  made  by  me  in  1891.  A  patient  with  an  aortic  aneurysm,  which  had 
perforated  externally  and  given  rise  to  repeated  losses  of  blood,  died  sud- 
denly without  renewed  haemorrhage.  At  the  autopsy,  made  in  cool  weather 
eight  hours  after  death,  there  was  abundant  odourless  gas  in  the  heart  and 
vessels  without  a  trace  of  cadaveric  decomposition  anywhere  in  the  body. 
It  was  proven  that  the  gas  was  generated  by  an  anaerobic  bacillus,  which 
was  studied  by  Dr.  Nuttall  and  myself,  and  named  by  us  Bacillus  aerogencs 
capsulatus.  This  bacillus  is  identical  with  one  subsequently  found  by 
E,  Fraenkel  in  gaseous  phlegmons,  and  with  that  found  by  Ernst  and 
others  in  livers  which  are  the  seat  of  post-mortem  emphysema  (Scliaum- 
leber).  It  is  widely  distributed  in  the  outer  world,  being  present  especially 
in  the  soil,  and  often  exists  in  the  human  intestinal  canal.  Dr.  Flexner 
and  I  have  reported  twenty-three  personal  observations  in  which  this  gas- 
bacillus  was  found,  and  since  our  publication  we  have  met  with  several 
additional  ones.  The  only  points  concerning  these  cases  which  here  concern 
us  are,  that  this  bacillus  not  only  may  produce  gas  in  cadavers,  but  may 
invade  the  living  body,  and  cause  a  variety  of  affections  characterised  by 
the  presence  of  gas.  There  is  evidence  that  the  bacilli  may  be  widely  dis- 
tributed by  the  circulation  before  death,  and  that  gas  generated  by  them 
may  be  present  in  the  vessels  during  life.  In  most  cases,  however,  in  which 
this  bacillus  was  present,  the  gas  found  in  the  heart  and  blood-vessels  was 
generated  after  death.  I  do  not  consider  that  there  is  satisfactory  evidence 
that  similar  effects  may  be  produced  by  the  colon  bacillus,  as  has  been 
asserted.  There  is,  however,  a  facultative  anaerobic  bacillus,  very  closely 
allied  to  B.  aerogenes  capsulatiis,  which  may  also  cause  gaseous  phleg- 
mons and  produce  gas  in  the  vessels  aft«r  death. 

Our  observations  have  demonstrated  that  the  finding  of  gas-bubbles  in 
the  heart  and  vessels  a  few  hours  after  death  without  any  evidence  of 
cadaveric  decomposition  is  no  proof  that  the  gas  is  atmospheric  air,  or  is  not 
generated  by  a  micro-organism.  In  all  such  cases  a  bacteriological  exami- 
nation is  necessary  to  determine  the  origin  of  the  gas.  In  many  cases 
report^'d  as  death  entrance  of  air  into  the  veins,  the  evidence  for  this  con- 
clusion has  been  nothing  more  than  finding  gas-bubbles  in  the  heart  and 
vessels  after  sudden  or  otherwise  unexplained  death.  In  the  absence  of  a 
bacteriological  examination,  the  only  cases  which  can  be  ai-cepted  as  con- 
clusive are  those  in  whicli  deatli  has  occurred  immediately  or  shortly  after 
the  actually  observed  entrance  of  a  considerable  amount  of  air  into  the 
veins.     There  have  been  a  number  of  carefully  observed  and  indisputable 


EMBOLISM  225 

instances  in  wliich  during  a  surgical  operation  in  the  "  dangerous  region  " 
life  was  imperilled  or  extinguished  by  the  demonstrated  entrance  of  air 
into  wounded  veins.  After  the  audible  sound  of  the  suction  of  air  into  the 
vein,  death  was  sometimes  instantaneous;  or  it  occurred  in  a  few  minutes 
after  great  dyspnoea,  syncope,  dilatation  of  the  pupils,  pallor  or  cyanosis, 
occasionally  convulsions,  sometimes  the  detection  by  auscultation  over  the 
heart  of  a  churning  sound  synchronous  with  the  cardiac  systole,  and  the 
exit  from  the  wounded  vein  of  blood  containing  air-bubbles.  These  very 
alarming  symptoms  may  disappear  and  the  patient  recover. 

The  evidence  for  this  mode  of  death  would  seem  to  be  almost  as  conclusive 
for  a  certan  number  of  the  sudden  deaths  following  injections  into  the  uterus, 
especially  for  the  purpose  of  committing  criminal  abortion,  and  after  the 
separation  of  placenta  praevia.  But  I  am  sceptical  as  to  this  explanation  of 
many  of  the  deaths  which  have  been  reported  as  due  to  the  entrance  of  air 
into  the  uterine  veins.  In  the  reports  of  Dr.  Flexner  and  myself  \vill  be 
found  the  description  of  several  cases  of  invasion  of  B.  aerogenes  capsu- 
latiis,  which  without  bacteriological  examination  would  have  the  same  claim 
to  be  regarded  as  deaths  from  entrance  of  air  into  the  uterine  veins  as  many 
of  those  so  recorded.  I  have  had  the  opportunity  to  examine  the  museum 
specimen  of  a  uterus  of  a  much-quoted  case  so  reported,  and  I  found  in  its 
walls  bacilli  morphologically  identical  with  our  gas-bacillus.  Certainly  all 
cases  of  this  kind  should  hereafter  be  reported  only  after  a  bacteriological 
examination,  Jiirgensen's  cases  of  supposed  entrance  of  gas  into  the  general 
circulation  through  the  gastic  and  the  intestinal  veins  are  imdoubtedly 
instances  of  invasion,  either  before  or  after  death,  of  gas-forming  bacilli. 

Since  Paul  Bert's  researches,  the  symptoms  and  death  which  occasionally 
follow  the  rapid  reduction  of  previously  heightened  atmospheric  pressure 
upon  exit  from  a  caisson  or  diver's  apparatus,  have  been  plausibly  attributed 
to  the  liberation  of  bubbles  of  nitrogen  in  the  circulating  blood.  This  expla- 
nation of  the  phenomena  is  not,  however,  free  from  doubt,  and  it  is  difficult 
to  bring  conclusive  evidence  in  its  support  in  the  case  of  human  beings. 
Little  weight  can  be  attached  at  present  to  the  reports  of  finding  bubbles  of 
gas  in  the  blood-vessels  of  those  who  hfive  died  from  caisson-disease,  for  these 
reports  have  not  hitherto  been  accompanied  by  any  bacteriological  examina- 
tion to  determine  the  source  of  the  gas. 

Ewald  and  Robert  have  made  the  curious  observations  that  the  limgs  are 
not  air-tight  under  an  increase  of  intrapulmonary  pressure  which  may 
temporarily  occur  in  human  beings.  They  foimd  in  experiments  on  animals 
that  small  air-bubbles  may  appear  under  these  circumstances  in  the  pul- 
monary veins  and  left  heart  without  any  demonstrable  rupture  of  the  pul- 


226  EMBOLISM 

monary  tissue;  and  they  argue  that  this  may  occur  under  similar  conditions 
in  human  beings.  The  entrance  into  the  circulation  of  a  few  minute  air- 
bubbles  in  this  way  would  doubtless  produce  no  effects.  Ewald  and  Kobert 
cite  two  or  three  not  at  all  convincing  published  cases  in  support  of  the 
possibility  of  death  resulting  from  the  entrance  of  air  through  unruptured 
pulmonary  veins.  Very  plausible  is  Janeway's  hypothesis  that  the  transitory 
hemiplegia  and  other  cerebral  symptoms,  which  have  occasionally  been 
observed  to  follow  wiishing-out  the  pleural  cavity  with  peroxide  of  hydrogen, 
or  some  other  procedure  by  which  air  or  gas  may  accumulate  in  this  cavity 
under  high  pressure,  are  due  to  air  embolism  or  gaseous  embolism  of  the 
cerebral  vessels. 

Not  less  remarkable  are  the  experimental  observations  of  Lcwin  and  Gold- 
schmidt  concerning  air-embolism  following  injections  of  air  into  the  bladder 
and  its  passage  into  the  ureters  and  renal  pelves.  It  has  not  been  demon- 
strated that  the  same  phenomenon  can  occur  under  similar  conditions  in 
human  beings. 

Fat  Embolism. — Fat  embolism,  first  observed  in  human  beings  by  Zenker 
and  by  Wagner  in  1862,  is  the  most  common  form  of  embolism;  but  its 
practical  importance  does  not  correspond  to  its  frequency.  It  is  of  greater 
surgical  than  medical  interest,  inasmuch  as  the  severer  forms  are  nearly 
always  the  result  of  traumatism.  The  usual  conditions  for  its  occurrence 
are  (i.)  rupture  of  the  wall  of  a  vessel  (ii.)  proximity  of  liquid  fat,  and 
(iii.)  some  force  sufficient  to  propel  the  fat  into  the  vessel. 

Fat-embolism  probably  occurs  in  every  case  of  fracture  of  bone  containing 
fat-marrow.  When  the  bone  is  rarefied,  and  contains  an  unusual  quantity 
of  fat-marrow,  embolism  resulting  from  its  injury  may  be  very  extensive; 
as  is  illustrated  by  several  fatal  cases  of  fat-embolism  following  the  forcible 
rupture  of  adhesions  in  an  anchylosed  joint.  Ribbert  has  shown  that  fat- 
embolism  may  result  from  simple  concussion  of  bone,  as  from  falls  or  a  blow. 
IntUimmations,  ha>morrhages  and  degenerations  of  tlie  osseous  marrow  may 
cause  it.  It  may  likewise  result  from  traumatic  lesions,  necroses,  haemor- 
rhages, inflammation  of  adipose  tissue  in  any  part  of  the  body, — of  the  brain, 
of  a  fatty  liver,  in  a  word  of  any  organ  or  part  containing  fat.  Injury  to  the 
pelvic  fat  during  child-birth  leads  to  fat-embolism.  Oil-globules  in  the 
blood  may  come  from  fatty  metamorphoses  of  thrombi,  of  endothelial  cells 
and  of  atheromatous  plaques.  The  lipaemia  of  digestion  and  of  diabetes 
mellitus  has  not  been  generally  supposed  to  lead  to  fat-embolism,  but  Sanders 
and  Hamilton  have  observed  capillaries  filled  with  oil-globules  after  death 
from  diabetic  coma,  and  they  attribute  in  certain  cases  dyspntea  and  coma  in 
diabetes  to  this  cause. 


EMBOLISM  227 

In  the  groat  majority  of  cases,  fut-orabolism  is  entirely  innocuous,  and, 
unless  it  is  searched  for,  its  existence  is  not  revealed  at  autopsy,  and  then 
only  by  microscopical  examination.  Plugging  of  capillaries  and  small 
arteries  with  oil  may,  however,  be  so  extensive  and  so  situated  as  to  cause 
grave  symptoms  and  even  death.  More  moderate  j)lugging  may  aid  in  caus- 
ing death  in  those  greatly  weakened  by  shock,  haemorrhage,  or  other  causes. 
The  detection  of  fat-embolism  in  the  pulmonary  vessels  may  be  of  medico- 
legal value  in  determining  whether  injuries  have  been  inflicted  before  or 
after  death. 

The  deposition  of  fat-emboli  is  most  abundant  in  the  small  arteries  and 
capillaries  of  the  lung,  where  in  extreme  cases  the  appearances  of  microscopic 
sections  may  indicate  that  considerably  over  one-half  of  the  pulmonary 
capillaries  are  filled  with  cylinders  and  drops  of  oil.  In  rare  instances  of 
extensive  injury  the  amount  of  fat  in  the  blood  may  be  enormous,  so  that 
post-mortem  clots  in  the  heart  and  pulmonary  artery  may  be  enveloped  in 
layers  of  solidified  fat.  Some  of  the  oil  passes  through  the  puJmonary 
capillaries  and  blocks  the  capillaries  and  arterioles  of  various  organs ;  those 
which  suffer  most  being  the  brain,  the  kidneys,  and  the  heart.  The  extent  of 
the  embolism  in  the  aortic  system  varies  much  in  different  cases,  being  some- 
times slight,  at.  other  times  extensive.  Probably  the  force  of  the  circulation 
determines  the  amount  of  fat  which  passes  through  the  pulmonary  capillaries. 
Oil  once  deposited  may  be  again  mobilised  and  transferred  to  other 
capillaries. 

As  already  stated,  it  is  only  in  the  comparatively  rare  instances  of  extensive 
fat-embolism  that  effects  of  any  consequence  are  produced.  The  fat  itself  is 
perfectly  bland  and  unirritating,  although  it  may  be  accidently  associated 
with  toxic  or  infective  material.  The  lesions  and  symptoms,  when  present, 
are  referable  mainly  to  the  lungs,  the  brain,  the  heart,  and  the  kidneys. 
These  lesions  are  multiple  ecchymoses  (which  in  the  lungs  and  the  brain 
may  be  very  numerous  and  extensive),  pulmonary  oedema,  and  patchy  fatty 
degeneration  of  the  cardiac  muscle  and  of  the  epithelium  of  the  convoluted 
tubules  of  the  kidney.  Pulmonary  oedema,  referable  probably  to  paralysis  of 
the  left  heart,  is  common  with  extensive  fat  embolism  of  the  lungs.  Death 
may  undoubtedly  be  caused  by  fat-embolism  of  the  cerebral  vessels,  possibly 
also  by  that  of  the  coronary  vessels. 

The  symptoms  in  the  extreme  cases  are  quickened  respiration,  rapid  pros- 
tration, reddish  frothy  expectoration,  the  crepitations  of  pulmonary  cx^dema, 
small  frequent  pulse,  cyanosis,  and — with  cerebral  invasion.— coma,  vomiting, 
convulsions,  and  occasionally  focal  cerebral  symptoms.  The  temperature 
may  either  fall  or  rise.  Oil-globules  are  often  found  in  the  urine,  but  it  is 
still  an  open  question  whether  these  are  eliminated  through  the  glomerular 
capillaries,  many  of  which  are  often  filled  with  oil. 


228  EMBOLISM 

From  the  recent  investigations  of  Beneke  it  appears  that  the  oil  is  readily 
disposed  of,  in  small  part  by  saponification,  possibly  oxidation,  and  emulsion 
by  means  of  the  blood  plasma ;  but  in  larger  part  through  the  metabolic  and 
phagocytic  activities  of  wandering  cells  which  form  a  layer  around,  the  fat. 
The  saponifying  ferment — lipase — which  Hanriot  has  discovered  in  blood- 
serum  is  probably  one  of  the  agents  concerned  in  disposing  of  the  fat. 

Embolism  by  Parenchymatous  Cells. — This  is  in  general  of  more 
pathologico-anatoniical  than  clinical  interest,  and  therefore  need  not  be 
considered  here  in  detail.  As  has  been  shown  by  Lubarsch,  Aschoff,  and 
^faximow,  bone-marrow  cells,  with  large  budding  nuclei,  usually  undergoing 
degeneration,  may  often  be  found  lodged  in  the  pulmonary  capillaries  after 
injury  to  bone,  in  toxic  and  infective  diseases,  in  leucocythaemia,  and  in  asso- 
ciation with  emboli  of  other  parenchymatous  cells.  I  have  seen  them  in  large 
nimiber  in  capillaries  of  the  liver  in  a  ca.se  of  spleno-meduUary  leuco- 
cythaemia. 

Xext  in  frequency  are  emboli  of  liver-cells,  which  are  foimd  chiefly  in 
pulmonary  capillaries,  but  may  pass  through  an  open  foramen  ovale  so  as  to 
reach  capillaries  of  the  brain,  kidneys,  and  other  organs.  F.  C.  Turner  in 
1884  first  observed  liver-cells  within  hepatic  vessels;  and  later  Jiirgens, 
Klebs,  Schmorl,  Lubarsch,  Flexner,  and  others  noted  their  transportation  as 
emboli  after  injury,  haemorrhages,  and  necroses  of  the  liver,  and  with  especial 
frequency  in  puerperal  eclampsia.  Secondary  platelet-thrombi  are  usually 
formed  about  the  cells. 

Especial  significance  was  attached  by  Schmorl  to  the  presence  of  emboli 
of  placental  giant-cells  (syncytium)  in  the  pulmonary  capillaries  in  cases  of 
puerperal  eclampsia;  but  these  emboli,  although  frequent,  are  not  constant 
in  this  affection,  and  they  may  occur  in  pregnant  women  without  eclampsia 
(Lubarsch,  Leusden,  Kassjanow). 

To  the  group  of  parenchymatous  emboli  may  be  added  the  transport  of 
large  cells  from  tlie  spleen  to  the  liver  through  the  splenic  and  portal  veins. 
I  have  seen  large  splenic  cells  containing  pigment  and  parasites  blocking  the 
capillaries  of  the  liver  in  cases  of  malaria ;  and  also  the  well-known  large 
sfilenic  cells  containing  red  blood-corpiL'^cles  in  cases  of  malaria  and  of 
typhoid  fever.  The  crescentic  endothelial  cells  of  the  spleen  may  enter  the 
circulation. 

After  traumatism  and  parenchymatous  embolism  fragments  of  osseous  and 
medullary  tissue  may  be  carried  to  the  pulmonary  vessels  as  emlx)li 
(Lubarsch,  Maximow).  Emboli  of  large  masses  of  hepatic  tissue  have  been 
found  in  branches  of  the  pulmonary  artery  by  Schmorl,  Zenker,  Hess,  and 
Gaylord  as  a  result  of  traumatic  laceration  of  the  liver.  Chorion-villi  may 
be  detached  and  very  rarely  conveyed  as  emboli  to  the  lungs  (Schmorl),  or 


EMBOLISM  239 

by  retrograde  transport  to  veins  in  the  vaginal  wall  (Neumann,  Pick). 
This  is  much  more  likely  to  occur  from  chorionic  carcinoma  and  moles  than 
from  a  normal  placenta. 

So  far  as  known,  emboli  of  marrow-cells,  of  liver-cells,  of  normal  syn- 
cytial cells,  and  of  splenic  cells  undergo  only  regressive  metamorphoses, 
which  lead  to  tlieir  eventual  disappearance.  The  possibility  that  without 
the  presence  of  any  syncytial  tumor  in  the  uterus  or  tubes,  emboli  of 
syncytial  cells  may  give  rise  to  malignant  tumours  with  the  typical  structure 
of  those  developing  from  syncytium,  seems  to  have  been  demonstrated  by 
a  case  reported  by  Schmorl ;  but  it  can  hardly  be  supposed  that  the  displaced 
syncytial  cells  were  normal.  Emboli  of  liver-cells  manifest  a  distinct 
coagulative  influence  (Hanau,  Lubarsch)  ;  and  in  two  instances  Lubarsch 
attributed  infarcts  in  the  kidney  and  the  liver  to  thrombi  formed  around 
these  cells.  Marrow-cells  and  syncytial  cells  may  likewise  cause,  in  less 
degree,  secondary  platelet  and  hyaline  thrombi ;  but  it  does  not  appear  tliat 
these  thrombi  have  the  importance  in  the  etiology  of  puerperal  eclampsia 
which  is  attached  to  them  by  Schmorl.  With  a  few  exceptions,  no  important 
lesions  of  the  tissues  or  definite  symptoms  have  been  conclusively  referred 
to  emboli  of  these  parenchymatous  cells. 

Although  widely  different  in  results,  the  transportation  of  tumour  cells 
by  the  blood-current  is  a  process  similar  to  that  of  parenchymatous  em- 
bolism, for  wliich  indeed  cellular  embolism  seems  to  me  a  preferable 
designation.  Benno  Schmidt  has  found  small  branches  of  the  pulmonary 
artery  plugged  with  cancer-cells  derived  from  gastric  cancer  or  its  metas- 
tases, both  with  and  without  growth  of  the  cells  into  the  walls  of  the 
plugged  arteries.  Such  cells  may  reach  the  lungs  by  conveyance  through 
the  thoracic  duct  and  innominate  vein. 

Embolism  of  Special  Arteries. — I  shall  present  the  salient  character- 
istics of  the  more  important  special  localisations  of  embolism,  so  far  as 
these  have  not  been  sufficiently  considered  in  the  preceding  pages,  or  do 
not  pertain  to  other  articles  in  this  work.  Embolism  of  the  central  nervous 
system  will  be  discussed  in  the  Volume  VIII  of  Allbutt's  "  Syst.  Med."  under 
"  Diseases  of  the  Brain  and  Spinal  Cord."  The  pygeniic  manifestations  of 
infective  embolism  have  been  described  in  the  articles  on  '^  Pyaemia"  (All- 
butt's  ''System  of  Medicine,"  I,  p.  601)  and  on  "Infective  Endocarditis" 
(Allbutt's  "  System  of  Medicine,"  I,  p.  626,  and  V,  p.  876). 

Pulmonary  Embolism. — The  effects  of  pulmonary  embolism  vary  with  the 
size  of  the  plugged  vessel,  the  rapidity  and  completeness  of  its  closure,  the 
nature  of  the  embolus,  and  associated  conditions.  Embolism  of  large,  of 
medium-sized  and  small  arteries,  and  of  capillaries  may  be  distinguished. 

The  most  frequent  source  of  large  emboli  is  peripheral  venous  thrombosis, 
although  they  may  come  from  the   right  heart.     Sudden  or  rapid  death 


230  EMBOLISM 

follows  embolism  of  the  trunk  or  of  both  main  divisions  of  the  pulmonary 
artery.  It  may  occur  also  from  embolism  of  only  one  of  the  main  divisions 
or  from  plugging  of  a  large  number  of  branches  at  the  hilum  of  the  lung. 

Death  may  be  instantaneous  from  syncope.  More  frequently  the  patient 
crieis  out,  is  seized  with  extreme  precordial  distress  and  violent  suffocation, 
and  dies  in  a  few  seconds  or  minutes.  Or,  when  there  is  still  some  passage 
for  tlie  blood,  the  symptoms  may  be  prolonged  for  hours  or  even  days  before 
the  fatal  termination.  The  symptoms  of  large  pulmonary  embolism  are  the 
sudden  appearance  of  a  painful  sense  of  oppression  in  the  chest,  rapid 
respiration,  intense  dyspnoea,  pallor  followed  by  cyanosis,  turgidity  of  the 
cervical  veins,  exophthalmos,  dilatation  of  the  pupils,  tumultuous  or  weak 
and  irregular  heart's  action,  small,  empty  radial  pulse,  great  restlessness, 
cold  sweat,  chills,  syncope,  opisthotonos,  and  convulsions.  The  intelligence 
may  be  preserved,  or  there  may  be  delirium,  coma,  and  other  cerebral  symp- 
toms. Particularly  striking  is  the  contrast  between  the  violence  of  the 
dyspna'a  and  the  freedom  with  which  the  air  enters  the  Imigs  and  the  absence 
of  pulmonary  physical  signs ;  unless  in  the  more  prolonged  cases  it  be  the 
signs  of  oedema  of  the  lungs.  Litten  found  in  two  cases  systolic  or  systolic 
and  diastolic  stenotic  murmurs  in  the  first  and  second  intercostal  spaces  on 
the  right  or  left  side  of  the  sternum.  In  prolonged  cases  tlie  symptoms  may 
be  paroxysmal  with  marked  remissions.  Eecovery  may  follow  after  the 
appearance  of  grave  symptoms.  There  has  been  much  and  rather  profitless 
discussions  as  to  the  degrees  in  which  the  symptoms  are  referable  to  asphyxia, 
to  cerebral  anaemia,  or  to  interference  with  the  coronary  circulation.  Doubt- 
less all  three  factors  are  concerned,  but  the  exact  apportionment  to  each  of 
its  due  share  in  the  result  is  not  easy,  nor  very  important. 

The  diagnosis  is  based  upon  the  sudden  appearance  of  the  symptoms,  with 
a  recognised  source  for  an  embolus.  It  is  surprising  to  find  in  the  larger 
statistics,  as  those  of  Bang  and  of  Bunger,  how  often  the  thrombosis  leading 
to  fatal  pulmonary  embolism  has  been  latent.  Here  the  diagnosis  cannot 
always  be  made;  but  in  many  cases  it  may  be  suspected,  or  l)e  reasonably 
certain  :  as  when  the  above-mentioned  symptoms  appear  in  ])uerperal  women ; 
during  convalescence  from  infective  fevers,  as  enteric  fever,  influenza, 
pneumonia;  in  marasmic  aiid  an;emic  conditions,  as  phthisis,  cancer,  chlo- 
rosis; after  surgical  operations,  especially  those  involving  the  pelvic  organs; 
and  in  persons  with  varicose  veins. 

Even  at  autopsies  the  source  for  the  embolus  has  sometimes  i)een  missed, 
but  this  has  been  due  generally  to  inability  or  failure  to  make  the  necessary 
dissection  of  the  peripheral  veins,  or  to  dislocation  of  the  entire  thrombus. 
Scrrc  has  published  a  series  of  cases  of  pulmonary  embolism  with  latent 
thrombosis,  sliowing  the  difficulties  which  may  attend  the  discovery  of  the 


EMBOLISM  231 

Bource,  and  the  frequency  with  which  patient  searcli  reveals  the  primary 
thrombus.  The  majority  of  plugs  in  the  trunk  or  main  divisions  of  the 
pulmonary  artery,  found  in  eases  of  sudden  death,  present  the  anatomical 
characters  of  emboli,  associated  perhaps  with  secondary  thrombi ;  but  there 
remain  a  certain  number  of  cases  of  sudden  or  gradual  death  from  primary 
thrombosis  of  the  pulmonary  artery,  or  from  thrombosis  extending  int«  a 
main  division  from  an  embolus  in  a  smaller  branch  (see  "Thrombosis," 
p.  167). 

Bland  embolism  of  medium-sized  and  small  branches  of  the  pulmonary 
artery  in  normal  lungs,  and  without  serious  impairment  of  the  pulmonary 
circulation,  usually  causes  no  symptoms  and  no  changes  in  the  parenchyma 
of  the  lungs.  Even  in  lungs  structurally  altered,  and  with  serious  disturb- 
ances of  the  circulation,  such  embolism  may  be  without  effects.  The  ex- 
planation of  the  harmlessness  of  the  majority  of  medium-sized  and  small 
pulmonary  emboli  is  that  the  collateral  circulation  through  the  numerous 
and  wide  pulmonary  capillaries  is,  under  ordinary  conditions,  quite  capable 
of  supplying  sufficient  blood  to  an  area  whose  artery  is  obstructed,  to  pre- 
serve its  function  and  integrity ;  and  that  the  pulmonary  tissue,  in  contrast 
to  the  brain  and  the  kidney,  is  relatively  insusceptible  to  partial  local  ansmia. 

Often  enough,  however,  medium-sized  and  smaller  branches  of  the  pul- 
monary artery  are  occluded  by  emboli  or  thrombi  under  conditions  where  the 
pulmonary  circulation  is  incapable  of  compensating  the  obstruction,  and 
then  the  result  is  hsemorrhagic  infarction  of  the  lung.  The  most  com- 
mon and  important  of  the  conditions  thus  favouring  the  production  of 
haBmorrhagic  infarction  is  chronic  passive  congestion  of  the  lungs  from 
valvular  or  other  disease  of  the  left  heart.  It  is  especially  during  broken 
compensation  of  cardiac  disease  that  hffimorrhagic  infarction  of  the  lungs 
occurs,  sometimes  indeed  almost  as  a  terminal  event.  Other  favouring  con- 
ditions are  weakness  of  the  right  heart,  fatty  degeneration  of  the  heart, 
general  feebleness  of  the  circulation,  pulmonary  emphysema,  infective  dis- 
eases. 

The  source  of  the  embolus  causing  pulmonary  haBmorrhagic  infarction  is 
oftener  the  right  heart  than  a  peripheral  thrombus.  Globular  thrombi  are 
often  formed  in  the  right  auricular  appendix  and  ventricular  apex  in  uncom- 
pensated disease  of  the  left  heart,  particularly  of  the  mitral  valve  (see 
"Thrombosis,"  p.  141).  The  infarction  may  be  caused  also  by  thrombosis 
of  branches  of  the  pulmonary  artery,  which  are  not  infrequently  the  seat 
of  fatty  degeneration  of  the  intima  and  of  sclerosis  in  cardiac  disease  and  in 
emphysema.  Thrombi  in  larger  branches  often  give  rise  to  emboli  in  smaller 
ones. 

Pulmonary  infarcts  are  usually  multiple,  more  frequent  in  the  lower  than 
the  upper  lobes,  and  occur  on  the  right  side  somewhat  oftener  than  on  the 


233  EMBOLISM 

left;  corresponding  thus  with  the  distribution  of  emboli.  Their  size  varies 
generally  from  that  of  a  hazel-nut  to  a  pigeon's  egg;  but  it  may  be  smaller 
or  much  larger,  up  to  half  or  even  an  entire  lobe.  They  are  conical  or  of  a 
wedge-shape,  the  base  being  at  the  pleura.  Infarcts  are  rarely  buried  in  the 
substance  of  the  lung  so  as  to  be  invisible  from  the  pleural  surface.  Typical 
fresh  infarcts  are  strikingly  hard,  sharply  circumscribed,  swollen,  upon 
section  dark  red,  almost  black,  smooth  or  slightly  granular,  and  much  drier 
than  ordinary  hsemorrhages.  Examined  microscopically,  the  air-cells, 
bronclii,  and  any  loose  connective  tissue  which  may  be  included  in  the  infarct 
are  stuffed  full  of  red  corpuscles.  The  capillaries  are  distended,  and  in  all 
but  the  freshest  infarcts  usually  contain,  in  larger  or  smaller  amount,  hyaline 
thrombi,  to  which  von  Recklinghausen  attaches  mucli  importance  in  the 
production  of  the  infarct.  Fibrin  may  be  scanty  in  very  recent  infarcts,  but 
in  older  ones  it  is  abundant.  The  walls  of  the  alveoli  in  the  central  part  of 
the  infarct  are  the  seat  of  typical  coagulative  necrosis  with  fragmentation 
and  solution  of  the  nuclear  chromatin.  It  is  probable  that  the  red  corpuscles 
also  undergo  some  kind  of  coagulative  change,  for  otherwise  it  is  difficult 
to  explain  the  extremely  hard  consistence  of  the  fresh  infarct.  It  is  possible 
that  small  pulmonary  infarcts  and  very  recent  ones  may  occur  without 
necrosis;  but  the  ordinary  ones  are  necrotic,  and  cannot  therefore  be  re- 
moved by  resolution ;  but,  if  the  patient  lives  long  enough  and  suppuration 
or  gangrene  of  the  infarct  does  not  ensue,  are  substituted  by  cicatricial  tissue 
(Willgerodt). 

Ever  since  the  first  admirable  description  of  hemorrhagic  infarcts  of  the 
lungs  by  Laennec  there  has  been  considerable  difference  of  opinion  as  to 
their  explanation.  The  doctrine  that  they  are  usually  caused  by  emboli, 
however,  gradually  gained  general  acceptance.  This  explanation  has  al- 
ways had  opponents,  chiefly  on  the  grounds  that  emboli  often  occur  in  the 
pulmonary  arteries  without  infarction;  that  infarction  is  not  always  asso- 
ciated with  obstruction  of  the  corresponding  artery;  that  some  have  believed 
that  simple  haemorrhages  may  produce  the  same  appearances,  and  that  until 
recently  attempts  to  produce  pulmonary  infarction  experimentally  have 
been  without  positive  or  at  least  sufficiently  satisfactory  results.  Hamilton 
is  strongly  opposed  to  the  embolic  explanation,  and  attributes  haemorrhagic 
infarction  of  the  lung  to  a  simple  apoplexy,  resulting  usually  from  rupture 
of  the  alveolar  capillaries  in  chronic  passive  congestion.  Grawitz,  likewise, 
considers  that  embolism  has  nothing  to  do  with  the  causation  of  pulmonary 
infarction,  which  he  explains  by  haemorrhage  from  newly-fomied,  richly- 
vascularised,  peribronchial,  subpleural,  and  interlobular  connective  tissue 
consecutive  to  the  chronic  bronchitis  of  cardiac  and  other  diseases.  He 
emphasises  structural  changes  in  the  lung  as  an  essential  pre-requisite  for 


EMBOLISM  233 

infarction,  Grawitz's  attack  especially  has  stimulated  investigation  which, 
in  my  opinion,  has  strengthened  the  supports  of  the  embolic  doctrine  of 
haemorrhagic  infarction. 

The  evidence  seems  to  me  conclusive  that  pulmonary  infarcts  are  caused 
by  embolism  and  tlirombosis  of  branches  of  the  pulmonary  artery.  In  the 
great  majority  of  cases  the  arteries  supplying  the  areas  of  infarction  are 
plugged.  Upon  this  point  my  experience  is  in  accord  with  that  of  von  Reck- 
linghausen, Orth,  Hanau,  Oestreich,  and  many  others.  That  these  arterial 
plugs  are  secondary  to  the  infarction  is  improbable,  as  haemorrhages  else- 
where, as  well  as  undoubted  ones  in  the  lungs,  often  as  they  cause  secondary 
venous  thrombosis,  rarely  cause  arterial  tlirombosis.  Moreover,  there  is 
sometimes  an  interval  of  open  artery  between  the  plug  and  the  infarct,  a 
relation  not  observed  with  tlie  midoubtedly  secondary  thrombosis  of  veins 
connected  with  the  infarct,  and  not  explicable  on  the  assumption  that  the 
arterial  thrombosis  is  secondary'.  The  plug  often  has  the  characters  of  a 
riding  embolus.  Not  a  few  of  the  plugs,  however,  are  primary  thrombi.  The 
occasional  occurrence  of  pulmonary  infarction  without  obstruction  in  the 
arteries  has  as  much,  but  no  more,  weight  against  the  embolic  explanation  as 
the  similar,  and  I  believe  quite  as  frequent,  occurrence  of  splenic  infarcts 
without  embolism  or  thrombosis  of  the  splenic  arteries.  Both  the  haemor- 
rhage and  the  necrosis  of  infarcts  are  essentially  capillary  phenomena,  each 
being  independent  of  the  other ;  and,  undoubtedly  can  occur,  in  ways  little 
understood,  in  various  regions,  without  plugging  of  the  arteries. 

The  anatomical  characters  of  pulmonary  infarcts  are  essentially  the  same 
as  those  of  hasmorrhagic  infarcts  of  the  spleen  and  other  parts.  The  conical 
shape,  the  hard  consistence,  the  peripheral  situation,  the  coagulative  necrosis 
are  distinctive  characters  of  pulmonarv'  as  of  splenic  infarcts.  The  necrosis 
cannot  well  be  attributed  to  compression  of  the  alveolar  walls  by  the  ex- 
travasated  blood,  for  the  capillaries  in  these  are  usually  distended  widely 
with  blood.  It  has  the  general  characters  of  the  ischaemic  necrosis  of  infarcts, 
except  that  it  apparently  occurs  somewhat  later  in  the  formation  of  the  in- 
farct and  dogs  not  usually  reach  the  periphery;  phenomena  which  may  be 
explained  by  the  relative  tolerance  of  the  pulmonary  tissue  of  partial 
ischaemia,  and  by  a  better  peripheral  circulation  than  is  present  in  infarcts 
elsewhere. 

Inasmuch  as  emboli  do  not  ordinarily  cause  infarction  in  normal  human 
lungs  with  vigorous  circulation,  it  is  not  surprising  to  find  that  similar  emboli 
under  similar  conditions  do  not  cause  infarction  in  the  lungs  of  anmials.  It 
is  not  easy  to  reproduce  experimentally  in  animals  the  conditions  under 
which  pulmonary  infarcts  occur  in  man ;  yet  there  have  been  several  valuable 
contributions  in  recent  years  to  the  experimental  production  of  pulmonary 
18 


234  EMBOLISM 

infarction  :  tliese  have  furnished  an  experimental  basis,  which,  if  not  all  that 
is  to  be  desired,  still  marks  a  distinct  advance  for  the  embolic  doctrine  of 
haemorrhagic  infarction  of  the  lung.  Pulmonary  infarcts,  in  all  essential 
respects  identical  with  those  in  human  lungs,  have  been  produced  by  experi- 
mental embolism  or  arterial  occlusion  by  Cohnheim  and  Litton,  Perl,  Kiit- 
tner,  Mogling,  Grawitx,  Klebs,  Gsell,  Sgambati,  Orth,  Zahn,  and  Fujinami. 
Most  of  these  experimental  infarcts  have  been  produced  under  conditions 
not  very  analogous  to  those  of  human  infarcts;  but  the  essential  fact  that 
typical  haemorrhagic  infarction  of  the  lung  may  be  caused  by  arterial  plug- 
ging has  been  experimentally  established.  Into  the  details  of  these  experi- 
ments it  is  impossible  here  to  enter. 

Whether  genuine  haemorrhagic  infarct*  of  the  lung  may  ever  be  caused 
by  simple  hasmorrhage  from  rupture  of  lilood-vessels  is  perhaps  an  open 
question.  At  present  this  mode  of  their  production  seems  to  me  undemon- 
strated  and  improbable,  so  that  I  hold  that  simple  pulmonary  apoplexies  and 
genuine  infarct*  should  be  clearly  distinguished  from  each  other.  Neither 
the  results  of  experimental  introduction  of  blood  into  the  trachea  (Perl  and 
Lippmann,  Sommerbrodt,  Notlmagel,  Gluzinski),  nor  the  appearances  of 
the  lungs  after  undoubted  bronchorrliagias,  pneumorrhagias,  and  suicidal 
cutting  of  the  trachea  support  the  opinion  that  aspiration  of  blood  from  the 
trachea  and  bronchi  causes  genuine  haBmorrhagic  infarction.  In  only  one 
of  Sommcrbrodt's  numerous  experiments  was  such  infarction  oljserved,  and 
this  he  regards  as  accidental.  The  explanation  of  this  exceptional  result  is 
probably  the  same  as  in  PerPs  experiment  witli  thrombosis  after  venesection 
and  anaemia. 

I  have  seen,  in  two  or  three  instances,  nearly  white  or  pale-red  fresh 
anaemic  infarcts  in  densely  consolidated  lungs.*  Even  when  caused  by 
bland  emboli  pulmonary  infarcts  are  exposed  to  the  invasion  of  bacteria 
from  the  air-passages;  and  such  bacterial  invasion  may  lead  to  suppuration 
or  gangrene.  Completely  cicatrised  pulmonary  infarcts  occur,  but  they  are 
not  common — life  being  usually  cut  short  by  the  associated  cardiac  disease 
before  tlie  infarct  is  healed. 

Haemorrhagic  infarction  of  the  lungs  may  be  entirely  latent;  often,  how- 
ever, the  diagnosis  can  be  made  during  life.  Tlie  affection  may  be  ushered 
in  by  a  chill  or  chilly  sensation,  increase  of  a  usually  existing  dyspna?a,  and 
localised  pain  in  this  side.  These  s}Tnptoms  are  far  from  constant.  The 
characteristic  syniptr)m,  ahhough  by  no  means  pathognomonic,  is  bloody 
expectoration.  Profuse  luemoptysis  was  noted  by  Lacnnec,  but  is  very  rare. 
The  sputum  contains  dots  and  streaks  of  blood,  or  small  dark  coagula;  or, 

*  In  very  rare  instances  pulmonary  infarcts  are  anaemic  in  consequence  of 
extreme  weakness  of  the  circulation  (87). 


EMBOLISM  235 

more  frequently,  the  blood  is  intimately  mixed  with  tlie  expectoration,  which 
is  in  small  masses  and  usually  less  viscid  and  darker  red  than  that  of  pneu- 
monia, although  it  may  resemble  the  latter.  Blood  may  be  present  in  the 
sputum  for  one  or  two  weeks  or  even  longer  after  the  onset  of  the  infarction. 
It  acquires  after  a  time  a  brownish-red  tint,  and  generally  contains  the  pig- 
mented epithelial  cells  usually  seen  in  the  sputum  of  chronic  passive  con- 
gestion. Circumscribed  sero-fibrinous  pleurisy  is  usually  associated  with 
pulmonary  infarction.  Even  with  infarcts  not  more  than  four  or  five  centi- 
metres in  diameter  the  physical  signs  of .  consolidation  and  subcrepitant 
rales  can  sometimes  be  detected ;  usually  in  tlie  posterior,  lower  parts  of  the 
lungs.  These  signs  are  referable  not  only  to  the  infarct,  but  also  to  the 
surrounding  localised  oedema  and  perhaps  reactive  pneumonia.  There  may 
be  moderate  elevation  of  temperature.  When  the  characteristic  bloody  ex- 
pectoration, together  with  signs  of  circumscribed  consolidation,  appears  in 
the  later  stages  of  cardiac  disease,  or  with  peripheral  venous  thrombosis, 
there  is  generally  little  doubt  of  tlie  diagnosis.  Yet  similar  expectoration 
may  occur  from  simple  bronchial  hasmorrhages  in  intense  passive  congestion 
of  the  lungs  without  infarction.  The  expectoration  in  cancer  of  the  lungs 
may  resemble  that  of  pulmonary  infarction. 

The  sudden  appearance  of  pain  in  the  chest,  cough,  and  elevation  of  tem- 
perature, immediately  after  the  hypodermic  injection  of  undissolved  prepa- 
rations of  mercury,  is  attributed  to  pulmonary  embolism.  The  symptoms 
disappear  in  a  few  days  witliout  serious  consequences.  This  complication 
has  been  rare  in  the  experience  of  most  of  those  who  have  employed  this 
treatment  of  syphilis,  but  has  led  some  to  abandon  the  method. 

The  embolic  pneumonias  and  abscesses  caused  by  infarctive  emboli  are 
pyfemic  manifestations,  and  have  been  considered  in  the  article  on  "  Pyaemia  " 
in  the  first  volume  of  Allbutt's  Syst.  iled. 

Splenic  Infarction. — Anaemic  infarcts  of  the  spleen,  whicli  are  commoner 
than  the  haemorrhagic  variety,  are  not  usually  in  the  recent  state 
so  pale  and  bloodless  as  those  of  the  kidney;  for  the  spleen  is  much 
richer  in  blood  tlian  the  kidney,  and  in  chronic  passive  congestion,  dur- 
ing which  the  larger  number  of  infarcts  occur,  the  red  pulp  contains  much 
blood  outside  of  the  vessels.  Many  of  these  infarcts  can  be  appropri- 
ately described  as  mixed  red  and  white  infarcts.  Splenic  infarcts  vary 
greatly  in  size,  but  in  general  they  are  much  larger  than  those  occurring 
under  the  same  conditions  in  the  kidney,  as  comparatively  large  arteries  in 
the  spleen  break  up  into  numerous  small  terminal  twigs.  Averaging  per- 
haps two  to  six  centimetres  in  diameter,  a  single  infarct  may  occur  one-half 
or  more  of  the  spleen.  The  recent  infarcts  are  hard,  swollen,  and  more  or  less 
wedge-shaped,  with  the  base  at  the  capsule,  which  is  often  coated  with  fibrin ; 


236  EMBOLISM 

or  in  older  cases  is  thickened  and  adherent  by  fibrous  tissue.  The  great 
majority  are  caused  by  emboli  from  the  left  heart  or  the  aorta;  but  both 
haemorrhagic  and  pale  splenic  infarcts  occur  without  arterial  occlusion; 
especially  in  certain  acute  infective  diseases;  oftenest  in  relapsing  fever,  but 
also  in  typhus,  enteric  fever,  cholera,  and  septicaemia.  The  causation  of  the 
latter  is  unknown.  Ponfick  attributes  them  to  venous  thrombosis,  which  may 
be  the  cause  of  the  haemorrhagic  infarcts;  but  it  is  difficult  to  understand 
how  it  can  produce  the  pale  anaemic  infarcts.  Bland  infarcts  are  mostly 
absorbed  and  substituted  by  pigmented,  occasionally  calcified,  scars,  which 
when  numerous  may  cause  a  lobular  deformity  of  the  spleen. 

Splenic  infarction  is  often  entirely  latent.  Of  the  symptoms  attributed 
to  it  chills  and  elevation  of  temperature  belong  usually  to  the  accompanying 
acute  or  chronic  endocarditis.  Swelling  of  the  spleen,  wliich  pertains  to 
chronic  passive  congestion,  is  produced  also  by  infarcts.  The  most  diagnostic 
value  attaches  to  the  sudden  appearance  of  pain  in  the  region  of  the  spleen, 
perhaps  increased  by  lying  on  the  left  side,  by  deep  inspiration,  and  by 
pressure;  and  to  a  perisplenitic  friction  rub,  which  can  sometimes  be  de- 
tected. These  sjonptoms  are  not  very  certain  diagnostic  points;  but  when 
they  occur  with  some  manifest  source  for  a  splenic  embolus,  and  perhaps  with 
recognised  embolism  in  other  organs,  they  justify  a  strong  suspicion  of 
splenic  infarction. 

Renal  Infarction. — Tliere  have  been  a  few  instances,  especially  after 
traumatism,  of  nearly  total  necrosis  of  a  kidney  from  thrombosis  of  the 
renal  artery,  combined  usually  with  thrombosis  of  the  vein.  Usually  plug- 
ging of  the  main  artery  leads  to  multiple  infarction  with  intervening  intact 
areas.  The  capsular  arteries  suffice  for  the  preservation  of  at  least  a  narrow 
outer  rim  of  renal  tissue. 

Renal  infarcts  are  nearly  always  ansemic,  in  the  recent  sbite  somewhat 
swollen,  and  of  an  opaque  pale  yellowish  colour,  with  the  base  of  the  wedge 
just  beneath  the  capsule  and  the  apex  toward  the  hiliun,  most  frequently  near 
the  boundary  between  the  pyramid  and  cortex.  Three  zones  can  often  be 
distinguished: — the  main  central  yellowish  wliite  mass  of  necrotic  tissue; 
next  to  this  a  narrow  yellow  zone  of  fatty  cells,  nuclear  fragments,  and 
disintegrating  leucocytes ;  and  an  outer,  irregular,  variable  rim  of  hyperaemia 
and  haemorrhage  which  belongs  partly  to  the  infarct  and  partly  to  the  sur- 
rounding tissue.  The  haemorrhage  may  extend  a  variable  distance  into  the 
infarct,  and  in  very  rare  instances  genuine  haemorrhagic  infarcts  occur  in 
the  kidney.  Numeroas  scars  from  old  infarcts  may  produce  a  form  of 
atrophic  kidney  to  which  the  epithet  embolic  is  applicable.  Thorel  finds  that 
a  limited  regeneration  of  the  epithelium  and  even  of  uriniferous  tubules  may 
occur  in  healing  renal  infarcts. 


EMBOLISM  237 

Very  large  infarcts  may  so  stretch  the  renal  capsule  as  to  induce  severe 
pain.  In  a  case  diagnosed  by  Traube  an  infarct  two  inches  in  diameter,  pro- 
jecting well  above  the  surface,  caused  intense  pain  and  tenderness  in  the 
region  of  the  infarcted  kidney,  \vith  extension  of  the  pain  into  the  corre- 
sponding thigh.  With  the  ordinary  small  infarcts  pain  is  not  usually  a 
prominent  symptom.  The  chief  sign  of  diagnostic  value  is  the  sudden 
appearance  of  blood  in  the  urine  in  association  with  disease  of  the  left  heart, 
aortic  aneurysm,  or  other  recognised  source  for  a  renal  embolus.  The 
amount  of  blood  is  usually  only  moderate  or  evident  by  microscopical  exami- 
nation of  the  urine.  It  is  to  be  remembered  that  chronic  passive  congestion 
of  the  kidney  is  itself  one  of  the  many  causes  of  haematuria.. 

Infective  emboli,  which  are  often  capillary  in  size,  cause  multiple,  often 
miliary  abscesses  in  the  kidney.  This  is  the  haematogenous  variety  of  acute 
suppurative  nephritis  which  occurs  often  in  acute  infective  endocarditis  and 
other  forms  of  pyemia.  Here  the  pyuria  and  other  renal  symptoms  are 
usually  of  less  consequence  than  those  of  general  infection. 

Embolism  and  Thrombosis  of  the  Mesenteric  and  Intestinal  Arteries. — 
Thrombosis  of  the  mesenteric  veins,  which  causes  lesions  and  symptoms 
identical  with  those  following  embolism  of  the  mesenteric  arteries,  has  been 
considered  in  the  preceding  article  (p.  178).  Since  Virchow's  first  descrip- 
tion of  embolism  of  the  superior  mesenteric  artery,  in  1847,  at  least  seventy 
cases  have  been  reported  of  embolism  or  thrombosis  of  the  mesenteric  arteries. 
The  affection,  although  not  common,  occurs  often  enough  and  is  of  such 
gravity  as  to  be  of  considerable  clinical  interest.  In  Watson's  collection  of 
cases  there  are  eight  which  occurred  within  a  single  year  in  Boston.  The 
casuistic  literature  upon  the  subject  is  fairly  extensive.  The  articles  of 
Litten  and  of  Faher  contain  reports  of  most  of  the  cases  published  up  to  1875. 
The  principal  clinical  features  were  carefully  studied  by  Gerhardt  and  by 
Kussmaul  in  1863-64.  The  papers  of  Watson  and  of  Elliot  in  1894-95  refer 
to  about  fifty  reported  cases,  of  which  they  have  analysed  those  with  satis- 
factory clinical  histories  with  special  reference  to  surgical  treatment.  The 
effects  of  occlusion  of  the  mesenteric  arteries  have  been  experimentally  studied 
by  Beckmannj  Cohn,  Litten,  Faber,  Welch  and  Mall,  and  Tangl  and  Harley. 

The  principal  conclusions  drawn  by  Mall  and  myself  from  our  experiments 
have  been  stated  already  in  the  discussion  of  the  collateral  circulation,  and  of 
ha?morrhagic  infarction  following  embolism  (pp.  205  and  212).  It  may 
here  be  repeated  that,  according  to  our  experiments,  the  blood  which  produces 
the  hsemorrhagic  infarction  enters  by  the  anastomosing  arteries  and  not  by 
reflux  from  the  veins;  that  the  luemorrhage  cannot  be  explained  by  any 
demonstrable  change  in  the  vascular  walls,  but  is  the  result  of  retardation 
and  stasis  of  the  circulation  and  clumping  of  red  corpuscles  in  the  veins  and 


238  EMBOLISM 

capillaries,  attributable  in  large  part  in  cases  of  arterial  obstruction  to  reduc- 
tion or  loss  of  lateral  pulsation  of  the  blood-current;  that  the  ischaemia  is 
increased  by  the  tonic  contraction  of  the  intestinal  muscle  which  follows  for 
two  or  three  hours'  closure  of  the  superior  mesenteric  artery;  and  that  the 
sudden  and  complete  shutting  off  of  the  direct  arterial  supply  to  a  loop  of 
intestine  5  to  10  ctm.  in  length  is  followed  by  haemorrhage  and  necrosis  of 
the  loop,  even  when  the  vessels  at  each  end  of  the  loop  are  open.  The^se 
results  we  obtained  by  experimentation  upon  dogs,  but  there  is  no  reason 
to  suppose  that  they  do  not  apply  to  human  beings.  With  the  exception  of 
Cohn,  the  other  experimenters  explain  the  infarction  by  regurgitant  flow 
from  the  veins  and  alterations  in  the  vascular  walls. 

The  majority  of  the  cases  of  hsemorrhagic  infarction  of  the  intestine  have 
been  due  to  embolism  of  the  mesenteric  arteries,  the  source  of  the  embolus 
being  usually  the  left  heart,  sometimes  an  antheromatous  aorta  or  aortic 
aneurysm,  and  in  one  instance  a  thrombus  in  the  pulmonary  veins  caused  by 
gangrene  of  the  lungs  ( Virchow) .  Several  cases  have  been  caused  by  autoch- 
tiionous  thrombosis  resulting  from  arterio-sclerosis,  aneurysm,  pressure, 
or  the  extension  of  a  thrombus  from  the  adjacent  aorta.  It  is  probable  that 
a  certain  nimiber  of  the  cases  reported  as  embolic  were  referable  to  primary 
thrombosis  of  the  mesenteric  arteries,  as  no  source  for  an  embolus  could  be 
discovered,  and  the  plugs  in  some  of  these  instances  were  fresh  adherent 
thrombi.  As  has  been  shown  in  the  preceding  article,  primar}'  thrombi  may 
form  in  arteries  which  are  free  from  atheroma  or  other  chronic  disease.* 

In  the  great  majority  of  the  cases  the  obstruction  was  in  the  superior 
mesenteric  artery.  The  few  scattered  instances  of  embolism  or  thrombosis 
of  the  inferior  mesenteric  artery  indicate  that  this  also  may,  very  rarely, 
cause  incomplete  liaemorrhagic  infarction  of  the  corresponding  part  of  the 
intestine,  but  that  the  collateral  circulation  here  is  better,  and  the  lesions 
likely  to  consist  only  in  small  haemorrhages  in  the  intestinal  mucosa.  The 
inferior  mesenteric  artery  may  be  obliterated  without  any  manifest  disturb- 
ance in  the  structure  or  function  of  the  })art  of  the  intestine  supplied  by  it. 

The  obstruction  may  be  situated  in  the  main  stem  or  in  any  of  the  branches 
of  the  superior  mesenteric  artery.    Intestinal  infarction  has  been  associated 

'  Litten  has  reported  two  cases  of  haemorrhagic  infarction  of  the  intestine  from 
thrombosis  caused  by  what  he  calls  "latticed  endarteritis"  (gitterformige  En- 
darteriitis)  of  the  mesenteric  arteries.  So  far  as  I  can  learn  he  has  not  furnished 
the  fuller  description  which  he  promised  in  his  article  of  nine  years  ago.  With- 
out such  description  there  is  room  for  the  suspicion  that  I^itten  has  mistaken  the 
latticework  markings  sometimes  seen  after  detachment  of  an  adherent  thrombus 
for  a  special  form  of  endarteritis.  It  does  not  appear  from  his  article  that  he  has 
observed  this  "  latticed  endarteritis  "  except  after  removing  adhertn  thrombi. 


EMBOLISM  239 

with  embolism  of  the  larger  branches  oftener  than  with  that  of  the  main 
stem.  As  the  anastomoses  through  the  arterial  arches  are  so  free,  obstruction 
of  single  small  branches  is  without  mechanical  effects.  There  have,  however, 
been  several  instances  of  intestinal  infarction  caused  by  multiple  emboli  or 
extensive  thrombosis  of  small  branches  of  the  superior  mesenteric  artery. 

Intestinal  infarction  is  not  the  imperative  result  of  occlusion  of  the 
superior  mesenteric  artery,  as  infarction  is  of  occlusion  of  branches  of  the 
splenic  and  renal  arteries,  and  of  the  basal  cerebral.  Both  the  trunk  and  the 
principal  branches  of  this  artery  may  be  gradually  closed  without  serious 
effects.  Tiedemann  and  Virchow  have  found  the  superior  mesenteric  artery 
completely  obliterated  by  old,  firm  thrombi  or  connective  tissue  without  any 
lesions  in  the  jejunum  or  ileum.  The  most  remarkable  case  is  that  of  Chiene, 
who  found  in  a  woman  sixty-five  years  old,  with  aneurysm  of  the  abdominal 
aorta,  complete  obliteration  of  the  cceliac  axis  and  both  mesenteric  arteries, 
with  an  adequate  collateral  circulation  through  the  greatly  distended  extra- 
peritoneal anastomosing  arteries.  In  a  nimaber  of  instances  plugging  of 
large  branches  of  the  superior  mesenteric  artery  has  caused  no  more  than 
hyperaemia  and  superficial  ecchymoses,  without  genuine  infarction  of  the 
intestine. 

The  rapid  and  complete  closure  of  the  superior  mesenteric  artery,  how- 
ever, is  followed  with  great  regularity,  probably  constantly,  by  haemorrhagic 
infarction  of  the  intestine.  There  have  been  several  instances  in  which 
embolism  or  thrombosis  of  the  trunk  of  this  artery  has  caiLsed  haemorrhagic 
infarction  extending  from  the  lower  part  of  the  duodenum  into  the  transverse 
colon  (Oppolzer,  Pieper,  Faber,  Kaufmann),  as  in  the  experimental  eases. 
More  frequently  the  infarction  is  in  the  lower  part  of  the  jejunum  and  the 
ileum,  corresponding  to  the  occlusion  of  a  principal  branch  or  of  several 
branches  supplying  this  region.  The  infarction  corresponds  in  general  to 
the  area  of  distribution  of  the  plugged  arteries,  but  it  may  occupy  only  a  part 
of  this  area.  In  several  instances  a  single  small  loop  or  several  loops  with 
intervening  normal  intestine  have  been  infarcted. 

As  already  intimated,  the  infarction  may  be  complete  or  only  partial. 
When  completely  infarcted,  the  wall  of  the  affected  intestine  is  thickened, 
cedematous,  of  a  dark  red  colour  from  infiltration  with  blood  and  covered 
with  lustreless  peritoneum.  The  margins  of  the  infarct  are  often  sharply 
marked  but  may  pass  gradually  into  the  normal  bowel.  The  mucous  mem- 
brane is  necrotic,  often  defective,  and  may  be  coated  with  a  diphtheritic 
exudate.  In  a  few  instances  the  intestine  has  been  gangrenous  over  consider- 
able areas,  without  typical  haemorrhagic  infarction,  or  with  the  haemorrhagic 
appearance  adjacent  to  the  gangrene.  The  lumen  of  the  intestine  contains 
black  tarry  blood.    There  is  bloody  fluid  in  the  peritoneal  cavity,  and  usually 


240  EMBOLISM 

a  fibrinous,  sometimes  a  fibrino-purulent  exudate  on  the  peritoneum  covering 
the  infarction;  and  there  may  be  general  peritonitis.  The  mesentery  is 
succulent  and  haemorrhagic,  usually  in  patches,  exceptionally  in  the  form  of 
large  flat  masses  of  extravasated  blood.  Areas  of  fat-necrosis  may  be  present 
in  the  mesentery.  The  mesenteric  veins  are  distended  and  the  mesenteric 
glands  often  swollen  and  haemorrhagic.  Various  intestinal  bacteria,  most 
commonly  the  colon  bacillus,  may  make  their  way  into  the  peritoneal  cavity 
through  the  necrotic  wall.  Flexner  and  I  have  reported  an  instance  of 
liiemorrhagic  infarction  of  the  jejimimi  in  which  e\idences  of  pneumo- 
peritonitis,  supposed  to  be  due  to  perforation,  existed  during  life.  At  the 
autopsy,  made  six  hours  after  death,  a  large  amount  of  gas  was  found  in  the 
peritoneal  cavity  without  perforation.  B.  aerogenes  capsulatus  was  present 
in  large  nimibers  in  the  peritoneal  exudate.  This  case  demonstrates  the 
generation  of  gas  in  the  closed  peritoneal  cavity.  In  the  intestinal  mucosa 
were  gas-blebs  which  were  observed  also  in  one  of  Faber's  cases  and  in 
Jiirgen's  case  of  intestinal  infarction. 

The  haemorrhagic  infarction  is  by  no  means  always  so  completely  formed 
as  that  just  described.  There  may  be  no  haemorrhages  in  the  mesentery. 
The  extravasation  of  blood  may  be  limited  to  the  mucosa,  or  even  to  the 
submucosa,  as  in  one  of  Ponfick's  cases.  In  an  instance  of  nearly  complete 
thrombosis  of  the  trunk  of  the  superior  mesenteric  arter)%  reported  by 
Councilman,  there  were  paralysis,  great  distension  and  ecchpnoses  of  the 
small  intestine,  but  no  infarction.  Between  mere  venous  hyperaemia  with 
scattered,  superficial  haemorrhages,  and  complete  necrosis  and  infarction, 
there  are  all  gradations,  the  controlling  factors  being  doubtless  the  rapidity 
and  extent  of  the  arterial  occlusion  and  the  vigour  of  the  general  circulation. 

There  have  been  two  or  three  instances  in  which  the  anatomical  picture 
of  haemorrhagic  infarction  of  the  intestine  has  been  present  without  dis- 
covery of  any  obstruction  in  the  corresponding  arteries  or  veins.  Lycett 
reports  an  observation  of  haemorrhagic  infarction  of  the  small  intestine  in 
an  infant  one  month  old  without  discoverable  cause. 

Haemorrhagic  infarction  of  the  bowel  may  be  insidious  in  its  onset  and 
course;  and,  in  patients  profoundly  prostrated  or  with  cerebral  symptoms, 
it  may  occur  without  the  attention  of  the  physician  being  drawn  to  any 
abdominal  trouble.  Usually,  however,  the  onset  is  abrupt,  and  grave  intes- 
tinal symptoms  are  present.  In  the  majority  of  cases,  severe  colicky  pain 
and  abdominal  tenderness,  either  without  distinct  localisation  or  most 
marked  near  the  umbilicus,  are  prominent  and  usually  the  first  symptoms. 
The  pain  at  the  beginning  is  perhaps  attributable  to  the  violent,  tonic  spasm 
of  the  intestine  which  follows  sudden  occlusion  of  the  superior  mesenteric 
artery.     After  a  few  hours  this  spasm  gives  place  to  complete  paralysis  of 


EMBOLISM  241 

the  affected  part  of  the  bowel,  and  then  the  pain  may  be  referable  to  peri- 
tonitis. The  local  anaemia,  hemorrhage,  and  necrosis  seem,  however,  quite 
sufficient  to  account  for  the  pain.  Vomiting,  which  often  becomes  bloody 
and  occasionally  faecal,  is  also  usually  an  early  and  persistent  symptom.  By 
far  the  most  characteristic  symptom,  which  is  present  in  the  majority  of 
cases  but  not  in  all,  is  the  passage  of  tarry  blood  in  the  stools,  which  are 
frequently  diarrhceal,  and  sometimes  have  the  odour  of  carrion.  In  nearly 
all  cases  there  is  haemorrhage  into  the  bowel,  but  the  blood  is  not  always 
voided.  Symptoms  of  intestinal  obstruction — tympimitic  distention  of  the 
abdomen,  faecal  vomiting  and  obstipation — are  in  some  cases  prominent, 
and  readily  explained  by  the  complete  paralysis  of  the  infarcted  bowel. 
The  subnormal  temperature,  pallor,  cold  sweats  and  collapse,  which  appear 
in  most  cases,  are  explicable  in  part  by  the  intestinal  haemorrhage,  and  in 
part  by  the  shock  of  the  destructive  lesion.  The  sensation  of  a  palpable 
tumour,  referable  to  a  coUeftion  of  Ijlood  in  the  mesentery  or  to  the  infarcted 
bowel,  has  been  noted  in  only  three  or  four  cases. 

The  chief  emphasis  for  purposes  of  diagnosis  is  to  be  laid  upon  the 
occurrence  of  intestinal  hEemorrhage,  not  expHcable  by  independent  disease 
of  the  intestine  or  by  portal  obstruction,  in  combination  with  other  symp- 
tom.s  mentioned,  and  with  the  recognition  of  some  source  for  an  embolus, 
perhaps  of  embolic  manifestations  elsewhere.  In  the  majority  of  cases  the 
diagnosis  has  been  intestinal  obstruction,  or  acute  peritonitis.  The  symp- 
toms closely  resemble  those  of  intussusception,  in  which  haemorrhage  from 
the  bowel,  although  generally  less  abundant  than  with  embolism  of  the 
superior  mesenteric  artery,  is  common.  Fortunately  the  distinction  of 
haemorrhagic  infarction  from  intestinal  obstruction  is  not  of  much  practi- 
cal importance;  for  if  the  symptoms  and  condition  of  the  patient  warrent 
it,  an  exploratory  laparotomy  is  indicated  in  both  conditions.  Elliot,  by 
the  successful  resection  of  four  feet  of  infarcted  intestine,  has  brought 
haemorrhagic  infarction  of  the  intestine  into  the  surgeon's  domain. 

The  prognosis  is  grave;  and  with  complete  infarction  and  necrosis  of 
the  intestine  it  is  almost  necessarily  fatal,  unless  surgical  relief  be  avail- 
able. Watson  estimates  that  in  about  one-sixth  of  the  cases  the  location 
and  extent  of  the  infarction  are  suitable  for  resection  of  the  bowel.  It  is 
impossible  to  say  at  present  to  what  extent  the  prognosis  of  haemorrhagic 
infarction  of  the  intestine  is  favourably  modified  by  the  new  possibilities 
of  surgical  interference.  Gordon  has  successfully  resected  two  feet  of 
infarcted  intestine.  This  and  Elliot's  case  are  the  only  two  in  which  this 
operation  has  been  performed ;  so  far  as  I  am  aware. 

When  the  infarction  is  incomplete,  and  is  limited  chiefly  to  the  inner 
coats  of  the  intestine,   recovery  may  doubtless  take   place.     Cohn,   Moos, 


243  EMBOLISM 

Lereboullet,  and  Finlayson  liave  reported  instances  of  rocovery  after  symp- 
toms indicative  of  hemorrhagic  infarction.  Packard  attributed  cicatrical 
areas  found  in  the  mesentery  of  an  ohl  man  dead  of  rupture  of  the  ascend- 
ing aortu  to  healed  infarction;  but  no  previous  history  was  obtained,  and 
Packard's  interpretation  does  not  seem  to  me  to  be  free  from  doubt.  Death 
may  occur  within  30  to  48  hours  after  the  onset,  or  the  duration  may  be  pro- 
tracted over  several  days.  Karcher  has  reported  the  sun'ival  of  a  patient 
with  mitral  stenosis  for  two  months  after  the  complete  occlusion  of  the 
superior  mesenteric  artery  by  an  embolus,  the  symptoms  being  sufficiently 
characteristic  to  have  permitted  a  probable  diagnosis  during  life. 

Intestinal  ulcers  due  to  embolism  or  thrombosis  constitute  a  distinct 
class,  which  has  been  studied  especially  by  Ponfick,  Parenski,  and  Noth- 
nagel.  Parenski  relates  an  instance  of  operation  for  intestinal  stricture, 
which  at  the  autopsy  was  found  to  be  caused  by  cicatrisation  of  an  ulcer 
due  to  embolism  of  a  branch  of  the  superior  mesenteric  artery.  Much 
more  common  are  ulcers  caused  by  infective  emboli  lodging  in  the  small 
arteries  and  capillaries  in  the  intestinal  wall;  they  are  observed  especially 
in  acute  ulcerative  endocarditis  and  pyajmia.  These  emboli  cause  haemor- 
rhages, necroses,  and  miliary  abscesses  with  resulting  ulceration.  The 
ulcers  are  usually  multiple,  sometimes  numerous,  and  situated  in  the  small 
intestine  and  wecum.  The  intestinal  ulcers  occasionally  associated  with 
degenerative  multiple  neuritis  are  referred  by  IMinkowski  and  Ix)renz 
to  thrombosis  caused  by  disease  of  the  small  arteries,  which  has  been 
repeatedly  observed  in  this  form  of  neuritis. 

Embolism  and  Thrombosis  of  the  Thoracic  Aorta. — Unless  there  be  some 
abnornuil  narrowing  or  obstruction  of  the  aorta,  it  is  hardly  possible  for 
an  embolus  to  lodge  in  this  vessel,  except  at  the  ostiimi  or  the  bifurcation. 
An  exception  to  this  rule  may  result  from  the  detachment  of  a  large 
aneurysmal  clot,  which,  as  in  three  ca.ses  of  abdominal  aneurysm  reported 
by  Bristowe,  may  block  the  aorta  at  or  just  below  the  mouth  of  the  aneurysm. 

I  know  of  but  three  instances  of  embolism  of  the  mouth  of  the  aorta — 
two  reported  by  Colin  with  instantaiUMius  death,  and  one  l)y  IJeid  in  whic-h 
the  patient  lived  an  hour  and  a  half  after  the  first  symptoms  of  partial 
obstruction. 

In  a  very  few  instances  the  liiincn  of  an  atheromatous  thoracic  aorta 
has  been  seriously  encroached  upon,  or  oven  obliterated,  hy  thrombotic 
masses.  Such  cases  have  been  report^'d  hy  Trost,  Tewat,  Carville,  Armet, 
Chvostek,  Jaurand,  and  Pitt.  The  thrombus  may  occupy  the  ascending, 
the  transverse,  or  the  descending  aorta,  and  may  occlude  the  mouths  of 
the  left  carotid  and  subclavian  arteries.  If  tliere  remain  a  sufficient  channel 
for  the  blood,  as  in  Pitt's  ca^c,  there  is  no  resulting  circulatory  disturbance; 


EMBOLISM  243 

otherwise  there  may  be  paralysis,  oedema,  gangrene  of  the  lower  extremities, 
and,  if  the  left  subclavian  is  obliterated,  of  the  corresponding  upi)er 
extremity. 

Bochdalek  and  Liittidi  have  each  described  an  instance  of  occlusion  of 
the  aorta  in  infants  by  the  extension  of  an  obliterating  thrombus  from  a 
dilated  ductus  Botalli.  Far  more  frequent  is  stenosis  or  atresia  of  the 
aorta  at  or  near  the  attachment  of  this  duct,  due  usually  to  persistence  of 
the  isthmus  aortae,  as  was  first  shown  by  Eokitansky.  Of  this  latter  condi- 
tion about  100  instances  have  been  recorded. 

Embolism  and  Thrombosis  of  the  Abdominal  Aorta. — Graham  in  1814 
referred  to  a  museum  specimen  in  Gla.sgow,  which  had  belonged  to  Allan 
Burns,  of  occlusion  of  the  abdominal  aorta  just  above  the  bifurcation  by 
old  laminated  coagulum  extending  into  the  iliacs.  I  have  found  fifty-nine 
subsequent  reports  of  occlusion  of  the  abdominal  aorta  by  embolism  or 
thrombosis,  and  have  seen  references  (which  I  have  not  consulted)  to  six 
or  seven  other  cases.'  I  have  not  included  in  this  list  the  detachment  of 
clots  from  abdominal  aneurysms,  although  Bristowe's  three  cases  demon- 
strate that  this  may  occasion  the  same  symptoms.  The  monographs  and 
articles  of  Meynard,  Cammareri,  Selter,  Roussel,  Charrier  and  Apert,  and 
Heiligenthal  contain  references  to  or  reports  of  forty-seven  cases ;  to  these 
I  have  added  twelve  published  cases  not  mentioned  by  them.  The  refer- 
ences are  at  the  end  of  this  article. 

Three  of  the  patients  were  living  at  the  time  of  the  reports,  and  in 
two  fatal  cases  there  was  no  autopsy.  In  the  remaining  fifty-four  the 
plug  occupied  the  lower  end  of  the  aorta  and  extended  a  variable  distance 
into  the  arteries  below.  In  thirty-one  the  plug  did  not  reach  higher  tlian 
tlie  inferior  mesenteric  artery;  in  ten  the  upper  extremit}'  lay  between 
the  inferior  mesenteric  and  the  renals;  in  three  between  the  renals  and  the 
superior  mesenteric;  in  two  between  the  latter  and  the  cceliac  axis;  in  one 
just  below  the  pillars  of  the  diaphragm,  and  in  seven  the'length  of  the  plug 
is  not  stated.  The  upper  part  was  often  conical;  so  that,  when  the  plug 
extended  higher  than  the  inferior  mesenteric,  it  was  often  not  obliterating 
until  at  or  below  this  artery.  In  the  great  majority  of  cases  only  tlie  last, 
or  the  last  two,  lumbar  arteries  were  blocked  by  the  thrombus.  In  sev- 
eral instances  a  thrombus,  either  independent  or  continuous  with  that  in 
the  aorta,  occupied  the  lumbar,  the  mesenteric,  the  renal,  or  other  branches 
of  the  aorta.     In  all   instances  the  thrombus  extended  into  tlie  common 

"  I  have  not  included  von  Weismayr's  case  (Wiener  med.  Presse,  1S94,  p.  1774), 
as  it  was  reported  while  the  patient  was  living,  and  in  the  discussion  some  doubt 
was  expressed  as  to  the  diagnosis;  nor  the  brief  mention  made  by  Teleky,  at  the 
same  time,  of  similar  observation. 


244  EMBOLISM 

iliacs,  and  in  many  into  arteries  lower  down,  sometimes  even  as  far  as 
the  posterior  tibial,  the  end  being  usually  lower  on  one  side  than  on  the 
other. 

It  is  difficult,  indeed  impossible,  from  the  published  descriptions,  which 
are  only  too  often  incomplete  and  unsatisfactory,  to  determine  accurately 
how  many  of  the  cases  were  referable  to  embolism  and  how  many  to  throm- 
bosis. Essentially  similar  cases  have  been  interpreted  differently  in  this 
respect  by  different  observers.  The  plug  was  usually  adherent,  and  only 
in  relatively  few  cases  were  its  anatomical  characters  such  (or  at  least  so 
described)  as  to  indicate  positively  its  nature  as  embolus  or  primary  throm- 
bus. The  majority  of  cases  with  sudden  or  rapid  invasion  of  character- 
istic symptoms  were  associated  with  cardiac  disease,  or  disease  of  the  upper 
part  of  the  aorta ;  and  would,  therefore,  naturally  be  interpreted  as  embolic. 
Still  in  many  of  these  no  satisfactory  source  for  a  large  embolus  was 
demonstrated.  Some  cases  not  less  abrupt  in  onset  were  without  any  affec- 
tion of  the  heart  or  of  the  aorta  above  the  plug.  The  sudden  appearance  of 
symptoms  of  obstruction  of  the  aorta,  although  strongly  indicative  of  embol- 
ism, are  not  decisive  upon  this  point.  Barth,  in  1848,  described  a  case  of 
obstruction  of  the  aorta  by  a  cylindrical  thrombus  extending  from  the 
superior  mesenteric  artery  to  the  bifurcation,  and  leaving  only  a  narrow 
channel  for  the  circulation  of  the  blood.  There  were  no  circulator}^  dis- 
turbances. If  this  narrow  channel  had  been  suddenly  closed  at  one  point, 
as  might  readily  happen,  the  symptoms  would  probably  have  been  those 
of  embolism.  It  is  evident  that  aortic  thromboses  secondary  to  only  partly 
oblitorative  emboli  riding  the  bifurcation  of  the  aorta,  or  to  emboli  or 
thrombi  in  the  iliacs  or  lower  arteries,  may  occasion  symptoms  like  those  of 
primary  thrombosis  of  the  aorta.  There  are  several  instances  of  such 
secondar}'  thrombosis  of  the  aorta  in  my  collection  of  cases. 

Without  nnicli  confidence  in  the  accuracy  of  the  classification  in  several 
instances,  I  have  divided  the  fifty-nine  cases  into  forty-five  referable  to 
embolism  of  the  aorta  at  the  bifurcation,  and  fourteen  due  to  thrombosis;  of 
the  latter,  seven  were  primar}%  six  secondary  to  embolism  of  the  iliacs, 
or  possibly  the  femoral,  and  one  to  thrombosis  of  the  arteries  of  the  extremi- 
ties. The  source  of  the  aortic  embolus  is  believed  to  have  been  the  heart  in 
thirty-five  cases;  aneurysm  of  the  ascending  aorta  in  one;  pressure  of  a 
tumour  on  the  aorta  in  two;  atheroma  of  the  thoracic  aorta  in  one;  in  six 
it  was  undetermined.  The  heart  was  found  to  be  normal  at  the  autopsy 
in  eleven  of  the  fifty-tliree  cases;  and  in  seven  both  the  iieart  and  the  aorta 
above  the  plug  were  normal. 

Mitral  stenosis  existed  in  twenty  cases  (two  of  these  being  caused  by 
thrombi  extending  from  the  left  auricle  into  the  ventricle),  acute  mitral 


EMBOLISM  245 

endocarditis  in  three,  mitral  endocarditis,  not  further  defined,  in  favour- 
mitral  insufficiency  without  stenosis  in  one,  thrombus  in  the  left  auricle 
without  valvular  disease  in  one,  thrombi  in  the  left  ventricle,  mostly  with- 
out valvular  disease,  in  eight,  and  large  aortic  vegetations  in  one. 

The  most  interesting  point  in  the  etiology  of  plugging  of  the  abdominal 
aorta,  so  far  as  it  is  permissible  to  draw  conclusions  from  so  few  instances, 
is  that  nearly  thirty-four  per  cent  of  the  cases  were  associated  with  mitral 
stenosis.  In  many  of  these  tlie  stenosis  was  extreme.  The  question  at 
once  arises  of  the  source  of  the  embolus  in  these  cases  for  it  cannot  be 
supposed  that  an  embolus  large  enough  to  occlude  the  lower  end  of  the 
aorta  could  pass  through  the  contracted  mitral  orifice.  Some  of  the  cases 
may  be  explained  by  a  smaller  emlx)lus  caught  at  the  aortic  bifurcation,  or 
in  an  artery  lower  down,  with  secondary  thrombosis  of  the  aorta;  but  the 
sudden  onset  of  motor  and  sensory  paraplegia  and  of  cessation  of  pulsation 
in  both  femoral  arteries  in  a  large  number  of  cases  seems  to  demand  abrupt 
stoppage  of  tlie  circulation  through  both  common  iliacs.  A  few  observers 
who  have  realised  the  difficulty  here  presented  have  assumed  that  a  large 
thrombus  had  formed  in  the  left  ventricle  and  been  detached  without  any 
trace  behind ;  for  only  in  two  or  three  of  the  cases  with  mitral  stenosis  was 
there  any  evidence  of  a  thrombus  in  the  left  ventricle  or  the  aorta  above 
the  plug.  This  explanation  must  be  regarded  as  purely  hypothetical.  The 
coexistence  in  a  number  of  these  cases  of  infarctions  of  the  spleen,  kidney, 
or  brain  has  seemed  to  some  writers  strong  evidence  in  favour  of  the  embolic 
nature  of  the  aortic  plug.  It  is  possible  that  the  explanation  even  of  the 
cases  with  acute  bilateral  symptoms  referable  to  aortic  obstruction  and 
associated  with  marked  mitral  stenosis  may  be  the  lodgment  of  a  small 
embolus  followed  by  thrombosis  of  the  aorta.  Although  in  the  classifica- 
tion above  given  I  have  placed  nearly  all  the  cases  with  mitral  stenosis 
under  embolism,  I  am  nevertheless  not  disinclined  in  spite  of  the  rapid 
onset  of  the  symptoms,  and  frequently  coexistent  infarctions,  to  interpret 
many  of  them  as  primary  thromboses  of  the  aorta.  The  circulator}^  con- 
ditions with  extreme,  uncompensated  mitral  stenosis  seem  favourable  to 
the  occurrence  of  arterial  thrombosis;  and,  if  this  view  lie  accepted  for  the 
plugging  of  the  abdominal  aorta,  the  question  arises  whether  thrombi  fre- 
quently present  in  smaller  arteries  in  association  with  this  form  of  valvular 
disease  may  not  oftener  be  primary  than  is  generally  supposed. 

In  a  few  cases  congenital  narrowing  of  the  aorta  was  noted.  In  three 
instances  plugging  of  the  abdominal  aorta  was  associated  ynth  embolism 
or  thrombosis  of  arteries  of  an  upper  extremity.  Coincident  thrombosis 
of  the  vena  cava,  iliac,  or  femoral  veins  was  observed  in  a  few  cases.  In 
Jiirgens'  patient  there  was  haemorrhagic  infarction  of  the  intestine.     In 


24  G  EMBOLISM 

Beveral  instances  haemorrhages  were  found  at  autopsy  in  tlie  mucous  mem- 
branes of  the  bladder  and  uterus.  Herter,  in  his  experiments  in  my  labora- 
tory witli  ligation  of  the  abdominal  aorta  in  rabbits,  found  haemorrhagic 
infarction  of  the  uterus  to  be  so  common  a  result  of  this  operation  that, 
when  it  was  desired  to  keep  the  animals  alive  for  any  length  of  time,  we 
abandoned  the  use  of  female  rabbits  for  Stenson's  experiment.  It  does  not 
appear,  however,  that  in  hiunan  beings  ha?morrhage  of  the  uterus  is  a  com- 
mon sequel  of  occlusion  of  the  abdominal  aorta.'  It  is  probable  that  if 
search  were  made  in  suitable  eases  in  human  beings  who  have  died  of  aortic 
thrombosis  or  embolism,  the  interesting  muscular  changes  described  by 
llerter  in  the  experimental  cases  would  be  found;  as  similar  changes  had 
been  previously  discovered  by  Litten  in  an  instance  of  occlusion  of  the 
right  iliac  and  femoral  arteries.  The  most  important  of  these  muscular 
alterations  are  vacuoli.sation,  proliferation  of  the  sarcolemma  nuclei,  atrophy, 
and  fatty  and  pseudo-waxy  degenerations. 

Plugging  of  the  abdominal  aorta  has  occuiTcd  most  frequently  in  the 
course  of  chronic  cardiac  or  arterial  disease;  but  in  some  instances  it  took 
place  during  or  after  an  acute  infective  disease,  as  acute  articular  rheu- 
matism, puerperal  fever,  erysipelas,  during  convalescence  from  enteric 
fever  (Forgues),  and  after  pneumonia  (T>*;yden). 

Of  tlie  fifty-nine  cases  thirty  were  females,  twenty-seven  males,  and  in 
two  the  sex  is  not  stated.  Seventeen  were  between  twenty  and  thirty  years 
of  age,  twelve  between  thirty  and  forty,  eight  between  forty  and  fifty, 
thirteen  between  fifty  and  sixty,  one  was  nineteen,  one  sixty-one,  and  the 
ages  of  seven  are  not  given."  Marked  atheromatous  changes  in  the  arteries 
were  noted  in  fourteen  cases.  Occlusion  of  the  abdominal  aorta  by  embolism 
or  thrombosis,  therefore,  is  not  especially  a  senile  affection. 

When  one  considers  the  manifold  conditions  under  which  tlie  abdominal 
aorta  may  become  partly  or  completely  plugged  by  embolism  or  by  primary 
or  secondary  thrombosis,  it  is  evident  that  there  can  be  no  general  imiformity 
of  symptoms.  The  plug  may  be  so  situated  as  to  interfere  with  the  circula- 
tion in  one  leg  more  than  in  the  other.  Diversities  arise  from  variations  in 
the  collateral  circulation  in  different  cases.     Still  tlie  majority  of  patients 

'  It  may  here  be  mentioned  that  Herxheimer,  Popoff,  and  Chiari  have  each 
described  an  instance  of  haemorrhagic  infarction  of  the  uterus  after  extensive 
bilateral  plugging  of  the  vessels  supplying  this  organ. 

•  In  Liittich's  case  already  mentioned  (p.  243)  of  the  thrombosis  of  the  aorta 
in  an  infant  fourteen  days  old,  a  thrombus  beginning  4  cm.  below  the  insertion 
of  the  ductus  Botalli  extended  into  the  iliac  arteries.  Charrier  and  Apert  include 
in  their  collection  of  reports  of  thrombosis  of  the  abdominal  aorta  two  cases 
from  Allibert's  thesis  of  1828,  one  three,  and  the  other  three  and  a  half  years 
old,  with  gangrene  of  one  leg.     I  have  not  counted  these  three  cases  in  my  list. 


EMBOLISM  247 

have  presented  a  well-characterised  group  of  symptoms.  In  the  larger 
number  of  cases  the  onset  has  been  acute,  in  the  minority  insidious  and  grad- 
ual. The  symptoms  have  often  appeared  simultaneously  in  both  legs,  but 
there  may  be  a  short  or  a  long  interval  between  the  invasion  of  one  and  that 
of  the  other  leg.  In  the  more  acute  cases  the  leading  symptoms  are  pain  in 
the  legs, — sometimes  in  the  loins  and  abdomen,  sudden  or  rapidly  mani- 
fested paraplegia,  anaesthesia  of  the  legs,  absence  of  femoral  pulsation,  and 
plienomena  of  mortification  extending  from  the  feet  upward.  In  several 
instances  the  patients,  while  wall<ing,  have  been  seized  with  excruciating 
pain  in  the  legs,  and  have  fallen  paralysed  to  the  ground.  The  pain  is  often 
atrocious  and  more  or  less  paroxysmal.  There  may  be  tenderness  on  pressure 
over  the  occluded  aorta.  In  a  few  cases  pain  has  not  been  a  prominent 
symptom. 

Although  the  paraplegia  ha.s  been  repeatedly  described  as  instantaneous 
in  its  appearance,  it  is  to  be  inferred  from  the  histories  of  carefully  observed 
patients  that  at  least  a  short  interval  of  time  and  sometimes  several  hours 
and  even  days  elapse  before  it  is  complete.  In  forty-four  cases  in  which 
there  are  definite  statements  about  the  motor  power,  there  was  complete  or 
nearly  complete  paraplegia  in  twenty-four;  incomplete  paralysis  of  both 
lower  extremities,  described  in  some  instances  merely  as  weakness,  in  ten ; 
paralysis  of  only  one  leg  in  five,  and  no  paralysis  in  five.  The  paralysis  seems 
to  be  usually  of  the  flaccid  variety,  but  in  some  cases  the  paralysed  muscles 
are  stiff.  In  Barie's  patient  the  paralysed  legs  were  completely  rigid,  and 
it  may  be  inferred  that  a  condition  analogous  to  rigor  mortis  had  set  in. 
With  complete  paralysis  the  reflexes  and  electrical  excitability  are  abolished. 
Paralysis  of  the  bladder  and  rectum,  with  retention  of  urine  and  involuntary 
evacuations,  was  observed  in  several  cases,  but  not  in  the  majority. 

Of  the  cases  witli  satisfactory  histories  in  only  two  was  there  no  disturb- 
ance of  sensation.  In  some  there  was  only  numbness  or  some  reduction  of 
sensation,  but  in  most  there  was  definite  anaesthesia,  extending  in  some  in- 
stances no  higher  than  the  knee, — more  frequently  to  the  middle  or  upper 
third  of  the  thigh,  and  in  two  cases  as  high  as  Poupart's  ligament.  There 
was  sometimes  complete  analgesia,  which,  however,  did  not  exclude  sensa- 
tions of  spontaneous  paiii  in  the  legs.  In  many  cases,  however,  there  was 
hyperalgesia,  either  in  the  anaesthetic  area  or  above  it. 

The  symptom  of  greatest  diagnostic  value  is  absence  of  pulsation  in  the 
arteries  of  the  lower  extremities.  In  three  or  four  instances  it  was  deter- 
mined that  the  abdominal  aorta  below  the  naval  was  pulseless.  Wilbur 
observed  excessive  aortic  pulsation  above  the  obstruction.  The  legs  become 
cold,  and  their  surface  temperature  may  even  fall  below  tliat  of  the  room 
(Browne,  Mauz).    Absence  of  bleeding  upon  incision  and  of  reactive  hyper- 


248  EMBOLISM 

femia  after  application  of  heat  have  been  noted.  The  skin,  at  first  pale,  soon 
acquires  a  livid  mottling,  and  the  superficial  veins  may  be  dilated.  (Edema 
of  one  or  both  legs  and  cutaneous  haemorrhages  are  recorded  in  some  of  the 
histories.  If  the  patient  lives  long  enough  gangrene  usually  ensues,  and 
it  may  be  manifest  within  twenty-seven  to  forty-eight  hours.  Gangrene  was 
bilateral  in  at  least  twenty-four  cases,  and  unilateral  in  seventeen.  The 
extent  of  the  gangrene  varied  greatly  in  different  cases,  being  sometimes 
limited  to  the  foot,  sometimes  reaching  the  middle  of  the  thigh,  and,  in 
Bell's  patient,  involving  the  scrotum.  Tympanites,  diarrhoea,  and  albumi- 
nuria are  common.  Exceptional  symptoms  are  the  appearance  of  blood  in 
the  urine  or  stools,  haematemesis,  and  priapism.  Bedsores  appeared  in  many 
cases,  and  may  appear  witliin  a  few  days  from  the  onset. 

Death  may  occur  within  twenty-four  hours  from  the  beginning  of  the 
attack.  Fourteen  patients  died  within  the  first  four  days,  with  collapse 
and  rapid,  weak,  usually  irregular  pulse.  There  may  be  marked  improve- 
ment in  the  initial  s}Tnptoms  either  in  one  or  in  both  legs.  The  larger  num- 
ber of  patients  die  after  a  variable  interval,  which  may  extend  over  several 
weeks  or  even  months,  from  gangrene,  decubitus,  and  sepsis. 

Of  the  deviations  from  the  type  may  be  especially  mentioned  incomplete 
manifestation  of  symptoms  on  one  or  both  sides,  transitory  affection  of  one 
leg,  limitation  of  the  symptoms  to  one  lower  extremity  only  (four  cases), 
and  affection  of  one  leg  followed  after  days,  weeks,  or  months  by  that  of  the 
other  (six  cases).  The  two  cases  reported  by  Barth  and  by  Jean  are  con- 
sidered particularly  characteristic  of  slowly  forming  thrombosis.  Here  the 
first  svTnptoms  were  chiefly  numbness  and  intermittent  claudication,  which, 
after  a  long  interval,  deepened  into  paraplegia  without  gangrene. 

All  but  three  cases  terminated  fatally,  more  frequently  from  the  remote 
effects  than  from  the  immediate  shock  of  occlusion  of  the  aorta.  The  three 
instances  of  survival  with  marked  amelioration  of  all  the  symptoms  are  re- 
ported by  Gull,  Chvostek,  and  Nunez.  These  eases  began  acutely  with 
severe  pains,  paraplegia,  disturbances  of  sensation,  coldness  and  lividity  of 
the  lower  extremities.  The  femoral  pulse  disappeared  completely  in  Gull's 
and  in  Nunez's  cases,  but  in  Chvostek's  it  could  still  be  felt,  although  it  was 
feeble.  In  Chvostek's  patient  patches  of  superficial  gangrene  appeared ;  but 
in  tiie  other  two  cases  there  was  no  gangrene.  Nunez  reports  that  after  a 
year  and  a  half  there  was  no  return  of  the  femoral  pulse  on  either  side. 

Since  the  demonstration  by  Schiffer  and  Weil,  confirmed  by  Ehrlich  and 

Brieger,  Spronck,  Horter,  and  others,  that  the  paraplegia  which   follows 

•immediately  or  very  shortly  after  ligation  of  the  abdominal  aorta  just  below 

the  renal  arteries  in  rabbits  (Stenson's  experiment)  is  due  to  ischaemia  of 

the  lumbar  cord,  many  have  assumed  that  the  same  explanation  applies  to 


EMBOLISM  249 

the  paraplegia  in  human  beings  after  occlusion  of  the  abdominal  aorta.  If 
the  rabbit's  aorta  be  tied  for  an  hour,  and  the  ligature  be  then  removed,  the 
paraplegia  and  paralysis  of  the  bladder  and  rectum  are  permanent,  the  gray 
matter  of  the  lumbar  cord  undergoes  necrosis,  and  a  genuine  myelitis  affect- 
ing chiefly  the  gray  but  also  the  white  matter  ensues.  The  same  experiment 
gives  negative  results  with  the  cat  and  usually  with  the  dog.  In  view  of  the 
great  interest  of  the  subject,  it  is,  to  say  the  least,  remarkable  how  few  of 
the  reports  of  autopsies  on  persons  dead  of  embolism  or  thrombosis  of  the 
aorta  have  anything  to  say  about  the  condition  of  the  spinal  cord.  Eoussel 
and  Heiligenthal  observed  no  macroscopic  changes  in  the  spinal  cord.  In 
Bell's  and  Barie  and  du  Castel's  cases  the  cord  was  microscopically  normal, 
save  congestion  in  the  latter.  Broca,  Legroux,  and  Malbranc  noted  with  the 
naked  eye  changes  in  colour,  from  which  no  definite  conclusions  can  be 
drawn.  The  only  detailed  report  of  a  microscopical  examination  of  the  cord 
is  that  of  Helbing,  who  found,  in  the  lumbar  region  of  a  man  who  lived 
thirty-nine  days  after  embolism  of  the  abdominal  aorta,  degeneration  of  the 
anterior  and  posterior  nerve-roots,  more  marked  on  one  side  than  the  other ; 
and  the  degenerations  in  the  cord  for  the  most  part  explicable  by  the  changes 
in  the  nerve-roots.  The  lesions  of  the  cord  were  quite  unlike  those  found  in 
experimental  cases,  and  are  interpreted  by  Helbing  as  essentially  analogous 
to  those  after  amputation,  and  not  referable  to  ischaemia  of  the  cord. 

As  the  matter  now  stands,  there  are  no  direct  observations  to  support  the 
opinion  that  the  paraplegia  following  embolism  or  thrombosis  of  the  abdomi- 
nal aorta  in  human  beings  is  caused  by  ischsemia  of  the  cord,  so  that  the  old 
explanation  which  refers  it  to  ischaemia  of  the  peripheral  nerves  and  muscles 
has  the  most  in  its  favor.  The  question  of  the  possibility  of  this  mode  of 
production  of  the  paraplegia,  however,  seems  to  me  still  open,  and  it  is  to  be 
hoped  that  hereafter  fatal  cases  of  this  rare  condition  will  not  be  reported 
without  satisfactory  microscopical  examination  of  the  spinal  cord.  The 
anatomical  investigations  of  Kadyi  and  of  Williamson  at  least  do  not  exclude 
the  possibility  that  the  lumbar  cord  in  human  beings  is  dependent  to  a  con- 
siderable extent  for  its  blood  supply  upon  the  lumbar  arteries. 

The  diagnosis  of  ischaemic  paraplegia  from  spinal  paraplegia  can  generally 
be  made  without  difficulty  by  the  absence  of  femoral  pulsation,  by  the  coldness 
and  lividity  of  the  extremities,  and  by  the  occurrence  of  gangrene  in  the 
former. 

Embolism  of  Arteries  of  the  Extremities. — Of  the  arteries  of  the  extremi- 
ties the  popliteal  and  the  femoral  are  the  most  frequent  recipients  of  emboli. 
The  results  of  embolism  of  arteries  supplying  the  extremities  are  essentially 
similar  to  those  of  arterial  thrombosis,  which  have  already  been  considered 
(p.  166).  The  modifications  resulting  from  the  sudden  advent  of  embolism 
19 


250  EMBOLISM 

are  sufficiently  self-evident.  There  may  be  severe  pain  at  the  moment  of 
impaction  and  at  the  site  of  lodgment  of  the  embolus.  The  general  principles 
involved  in  the  differentiation  of  embolism  from  thrombosis  have  been  pre- 
sented under  Diagnosis  (p.  221). 

Hepatic  Infarction. — As  the  effects  of  infective  emboli  in  branches  of 
the  portal  vein  and  of  the  hepatic  artery  have  been  considered  elsewhere 
in  this  work  (Allbutt's  "  System  of  Medicine,"  I,  p.  601,  and  V,  p.  123),  only 
the  possible  mechanical  effects  of  hepatic  emboli  require  consideration  here. 
Although  the  intrahepatic  branches  of  the  hepatic  arter}-  and  of  the  portal 
vein  are  terminal  vessels,  their  capillary  communications  arc  so  abundant 
tliat,  as  a  rule,  embolism  or  thrombosis  of  the  hepatic  vessels  causes  no  inter- 
ference T^-ith  the  circulation  in  the  liver.  Experiments  of  Cohnheim  and 
Litten  tmd  of  Doyon  and  Dufourt  have  demonstrated  that  complete  interrup- 
tion of  the  circulation  through  the  hepatic  arteries  of  the  rabbit  and  the  dog 
is  followed  by  necrosis  of  the  liver.  Chiari  has  obser\'ed  an  instance  of 
necrosis  of  tlie  entire  liver  caused  by  closure  of  the  trunk  of  the  hepatic 
artery  beyond  the  origin  of  the  pyloric  branch. 

In  rare  instances,  and  under  circumstances  at  present  not  thoroughly 
miderstood,  a  condition  somewhat  resembling  hjemorrhagic  infarction  may 
follow  plugging,  either  by  an  embolus  or  a  thrombus,  of  branches  of  the 
portal  vein.  Instances  of  this  occurrence  in  human  beings  have  been  re- 
ported by  Osier,  Eattone,  Klebs,  Lubarsch,  Kohler,  Pitt,  Zalm,  and  Chiari; 
the  last-named  having  seen  17  cases,  of  which  15  were  embolic.  A  somewhat 
similar  condition  was  observed  by  Arnold  after  retrograde  eml)olism  of  the 
hepatic  vein.  Pale  wedge-shaped  areas  have  been  observed,  but  in  most  of 
the  cases  there  were  circumscribed  dark  red  or  reddish-brown  wedge-shaped, 
rectangular  or  irregular  areas. 

Kohler  and  Chiari  found  that  the  red  colour  is  due  mainly  to  dilatation 
of  the  intralobular  capillaries,  with  atrophy  of  the  liver-cells.  Geniune  coagu- 
lative  necrosis  is  not  present.  The  affected  areas  are  patches  of  circumscri])ed 
red  atrophy  rather  than  typical  hemorrhagic  infarcts.  Zahn  observed  the 
same  condition  in  a  human  liver  after  plugging  of  portal  branches,  and  repro- 
duced it  experiniont^illy  by  emboli  of  sterilised  mercury*  injected  into  mesen- 
teric veins.  In  his  experimental  cases  the  change  in  the  liver  did  not  begin 
until  the  eighth  day,  and  was  distinct  after  thirty-five  days.  It  is  probable 
that  the  areas  do  not  undergo  cicatrisation. 

Rattone's  thcon,',  based  upon  experiments,  that  occlusion  of  branches  of 
both  the  hepatic  artery  and  portal  vein  is  essential  for  the  production  of 
infarction  of  the  liver,  is  not  supported  by  the  observations  in  human  beings. 
KU'bs,  whose  two  cases  followed  injury  of  the  liver,  as  was  true  also  of 
Lubarsch's  observation,  attributes  the  infarction  to  extensive  capillary  throra- 


EMBOLISM  251 

bosis.  Kohler  considers  that  the  essential  factor  is  combination  of  occlusion 
of  branches  of  the  portal  vein  with  obstruction  to  the  return  flow  from  the 
hepatic  veins.  Chiari  believes  that  the  second  factor,  to  be  added  to  the 
plugging  of  portal  branches,  is  feeble  flow  through  the  hepatic  artery,  from 
weakness  of  the  general  circulation,  Wooldridge,  by  injecting  coagulative 
tissue-extracts  into  the  jugular  vein  of  the  dog,  caused  extensive  clotting  of 
blood  in  the  portal  vein  and  its  branches,  followed  by  numerous  haemorrhages 
and  necroses  in  the  liver  r  but  the  interpretation  of  these  results  as  actual 
infarctions  does  not  seem  to  me  certain,  inasmuch  as  these  extracts  in  toxic 
doses  produce  a  haemorrhagic  diathesis,  and  may  cause  necroses  in  various 
situations  independently  of  thrombosis.  The  focal  necroses  so  often  met 
with  in  the  liver  in  various  infective  and  toxic  states  do  not  usually  stand  in 
any  definite  relation  to  closure  of  the  vessels  (Welch  and  Flexner). 

Embolism  of  the  Coronary  Arteries  of  the  Heart. — This  is  far  less  frequent 
than  thrombosis,  but  Marie's  position,  that  scarcely  more  than  one  or  two 
of  the  reported  cases  of  coronary  embolism  are  free  from  all  criticism,  seems 
to  be  too  extreme.  Metastatic  abscesses  in  the  heart  are  not  particularly  rare 
manifestations  of  pyaemia.  To  what  extent  they  are  caused  by  coarse  infective 
emboli,  or  by  the  lodgment  of  isolated  bacteria,  or  small  bacterial  clumps, 
does  not  appear  to  be  established.  The  heart  ranks  next  to  the  kidney  as  the 
most  frequent  seat  of  abscesses  following  intravascular  injection  of  the 
pyogenetic  staphylococci  in  rabbits. 

Virchow,  Chiari,  Eolleston,  Hektoen,  and  others  have  published  observa- 
tions of  bland  embolism  of  the  coronary  arteries.  I  have  observed  an  instance 
in  which  the  embolic  nature  of  the  plug  seemed  to  me  conclusively  established. 
A  woman,  36  years  old.  who  had  presented  symptoms  of  mitral  insuificiency, 
died  suddenly  after  a  paroxysm  of  dyspnoea  and  precordial  distress  lasting 
tAvo  or  three  minutes.  I  found  an  entirely  loose  grayish  plug,  4  nmi.  long, 
with  a  rough  irregular  extremity,  completely  occluding  the  descending  branch 
of  the  left  coronary  arterv'  near  its  origin.  There  was  no  atheroma  at  the 
site  of  lodgment  of  the  embolus,  although  there  were  a  few  patches  in  other 
parts  of  the  coronary  arteries.  The  segments  of  the  mitral  valve  were 
tliickened,  retracted,  and  beset  with  both  old  and  fresh  vegetations,  and 
globular  thrombi  were  present  in  the  left  auricular  appendix.  There  were 
also  fresh  vegetations  upon  the  aortic  valve.  There  were  infarcts  in  the  spleen 
and  kidneysw    There  were  no  fibroid  patches  or  infarction  in  the  myocardium. 

The  effects  of  embolism  of  the  coronary  arteries  are  like  those  of  throm- 
bosis, which  have  already  been  considered  (p.  168). 

Embolism  and  Thrombosis  of  the  Retinal  Vessels. — Plugging  of  the  retinal 
vessels  is  of  general  pathological  as  well  as  special  ophthalmological  interest, 
for  it  is  possible  to  observe  with  the  ophthalmoscope  the  circulatory  disturb- 


252  EMBOLISM 

ances  in  the  retina,  Ischaemia  and  stasis  follow  immediately  closure  of  the 
central  artery  of  the  retina  by  an  embolus.  Vision  is  lost  with  characteristic 
suddenness.  Both  the  arteries  and  the  veins  are  narrowed,  the  latter  being 
often  unequally  contracted.  Subsequently  the  veins  may  dilate  to  some 
extent,  especially  in  the  periphery  of  the  retina,  and  present  ampulliform 
swellings.  An  interesting  phenomenon  is  the  appearance  in  the  veins  of  an 
intermittent,  sluggish  stream  of  broken  cylinders  of  red  corpuscles,  separated 
by  clear  spaces ;  and  by  pressure  on  the  eye-ball  a  similarly  interrupted  cur- 
rent may  often  be  made  to  flow  through  arteries  and  veins.  This  appearance 
of  interrupted  columns  of  blood  is  evidently  similar  to  that  observed  by  Mall 
and  myseK  after  closure  of  the  superior  mesenteric  artery  and  previously 
described  (p.  212).  After  a  short  time  the  optic  papilla  becomes  pale  and 
gray,  and  the  retina,  especially  in  the  neighborhood  of  the  papilla  and 
macula,  assumes  an  opaque,  grayish  white,  oedematous  aspect,  Ha?morrhages 
are  exceptional.  A  characteristic  ophthalmoscopic  appearance  is  the  cherry- 
red  spot  in  the  centre  of  the  macula,  caused  by  the  red  colour  of  the  choroid 
shining  through.  There  may  be  more  or  less  return  of  the  circulation  with 
improvement  and  even  complete  restoration  of  vision ;  but  the  prognosis  as 
regards  sight  is  in  general  unfavourable,  as  atrophy  of  the  retina  and  of  the 
optic  nerve  is  likely  to  ensue.  The  prognosis  is  more  favourable  with  em- 
bolism of  branches  of  the  retinal  artery.  Here  multiple  haemorrhages  usually 
Occur. 

Thrombosis  of  the  central  retinal  vein  is  distinguished  from  plugging  of 
the  artery  especially  by  the  abundant  hamorrhagas.  With  occlusion  of  the 
central  artery  the  condition  is  anaemic  infarction,  and  with  plugging  of  the 
vein  haemorrhagic  infarction. 

There  is  some  difference  of  opinion  as  to  the  relative  frequency  of  embo- 
lism and  of  thrombosis  of  the  central  retinal  artery.  Of  129  cases  collected 
by  Fischer,  ninety-one  had  heart  disease;  whereas  Kem  reports  that  of 
twelve  cases  in  Haab's  clinic  only  two  had  demonstrable  cardiac  disease;  and 
of  eigbty-three  cases,  collected  from  the  records,  in  GQ  per  cent  there  was  no 
demonstrable  source  for  an  embolus.  The  latter  author,  therefore,  regards 
the  majority  of  plugs  in  the  central  artery  of  the  retina  as  primay  thrombi. 
The  generally  accepted  opinion,  however,  is  that  embolism  is  more  common 
than  thrombosis  of  the  retinal  arteries. 

Treatment. — In  the  preceding  pages  mention  has  been  made  of  the 
surgical  treatment  of  haomorrhagic  infarction  of  the  intestine  and  of  gan- 
grene of  the  extremities ;  and  under  "  Thrombosis  "  the  importance  of  pre- 
venting so  far  ius  may  Ix*  the  separation  of  emboli  has  been  cmphixsised.  The 
general  indications  in  the  treatment  of  embolism  are  essentially  similar  to 
those  already  considered  for  thrombosis  (p,  184). 


EMBOLISM  253 

REFERENCES 
See  footnote  to  References  to  Thrombosis,  p.  185. 

Historical 

1.  Cohn,  B.:   Klinik  d.  embol.  Gefasskrankh.    Berlin,  1860. 

2.  J.   Cohnheim:     Untersuch.   lib.   d.   embol.   Processe.      Berlin,    1872. 

3.  Idem:  Vorles.  iib.  allg.  Pathol.    Berlin,  1892. 

4.  Virchow:    Gesammelte  Abhandl.    Frankf.,  1856. 

Abebka:nt  Embolism 

5.  Arnold:    Virchow's  Archiv,  1891,  CXXIV,  p.  385. 

6.  Bonome:   Arch,  per  le  sc.  med.,  1889,  XIII,  p.  267. 

7.  Ernst:    Virchow's  Archiv,  1898,  CLI,  p.  69. 

8.  Firket:   Acad.  roy.  de  med.  de  Beige,  1890. 

9.  Flexner:    Bull.  Johns  Hopkins  Hosp.,  1896,  VII,  p.  173. 

10.  Hauser:    Miinch.  med.  Woch.,  1888,  XXV,  p.  583. 

11.  Heller:    Deutsch.  Arch.  f.  kl.  Med.,  1870,  VII,  p.  127. 

12.  Lubarsch:    Fortschr.  d.  Med.,  1893,  XI,  p.  805. 

13.  Lui:    Arch,  per  le  sc.  med.,  1894,  XVIII,  p.  99. 

14.  Ribbert:    Centralbl.  f.  allg.  Path.,  1897,  VIII,  p.  433. 

15.  V.  Recklinghausen:    Virchow's  Arch.,  1885,  C,  p.  503. 

16.  Rostan:    These.    Geneve,  1884. 

17.  Scheven:     Inaug.-Diss.     Rostock,  1894. 

18.  Schmorl:    Deutsch.  Arch.  f.  kl.  Med.,  1888,  XLII,  p.  499. 

19.  Schmorl:    Path.-anat.  Untersuch.  iib.  Puerp.-Eklampsie,  Leipz.,  1893. 

20.  Zahn:   Virchow's  Arch.,  1889,  CXV,  p.  71,  and  CXVII,  p.  1. 

Anatomical  Chabactebs 

21.  Fagge:    Trans.  Path.  Soc.  Lond.,  1876,  XXVII,  p.  70. 

Effects 

22.  Askanazy:   Virchow's  Arch.,  1895,  CXLI,  p.  42. 

23.  Bier:    Virchow's  Arch.,  1897,  CXLVII,  pp.  256  and  444;  1898,  CLIII,  pp.  306 

and  434. 

24.  Bryant:    Boston  Med.  and  Surg.  Journ.,  1888,  CXIX,  p.  400, 

25.  Cerfontaine:    Arch,  de  biol.,  1894,  XIII,  p.  125. 

26.  Davaine:    Trait6  des  entozoaires,  p.  406.     Paris,  1877. 

27.  Feltz:    Schmidt's  Jahrb.,  1870. 

28.  V.  Frey:    Arch.  f.  Physiol.,  1885,  p.  533. 

29.  Goldenblum:    Versuche  iib.  Collateralcirculation,  etc.     Inaug.-Diss.     Dorpat 

1889. 

30.  Koppe:    Arch.  f.  Physiol.,  1890,  Suppl.-Bd.,  p.  168. 

31.  Kossuchin:    Virchow's  Archiv,  1876,  KXVII,  p.  449. 

32.  Kiittner:    Hid.,  1876,  LXI,  p.  21,  1878,  LXXIII,  p.  476. 

33.  Lister:    Bull.  acad.  de  med.,  1878,  2nd  s.,  VII,  p.  640. 

34.  Litten:    Ztschr.  f.  kl.  Med.,  1880,  I,  p.  131. 

35.  Mall:    Johns  Hopkins  Hosp.  Reports,  I,  p.  37. 


25-4  EMBOLISM 

36.  Marchand:    Berl.  kl.  Woch.,  1894,  p.  37. 

37.  Nothnagel:    Ztschr.  f.  kl.  Med.,  1889,  XV.  p.  42. 

38.  Panski  and  Thoma:    Arch.  f.  exp.  Path.,  1893,  XXXI,  p.  303. 

39.  Fonfick:    Virchow's  Arch..  1873,  LVIII,  p.  528. 

40.  V.  Recklinghausen:    Handb.  d.  allg.  Path.  d.  Kreislaufs,  etc.    Stuttg..  1883. 

41.  Thoma:    Lehrb.  d.  path.  Anat.,  Th.,  I.    Stuttg..  1894. 

42.  Weigert:    Virchow's  Archiv,  1877,  LXX,  p.  486;  1878,  LXXII,  p.  250;   1880, 

LXXIX.  p.  104. 

43.  Idem:  Centralbl.  f.  allg.  Path..  1891.  II.  p.  785. 

44.  Welch:    "  Haemorrhagic  Infarction,"  Trans.  Assoc.  Amer.  Physicians,  1887, 

II,  p.  121. 

45.  Zielonko;    Virchow's  Arch.,  1873.  LVII,  p.  436. 

Embolic  Aneubtsms 

46.  Buday:   Ziegler's  Beitr.,  1891.  X,  p.  187. 

47.  Clarke:   Trans.  Path.  Soc.  London,  1896,  XLVII,  p.  24. 

48.  Duckworth:    Brit.  Med.  Journ.,  1890,  I,  p.  1355. 

49.  Eppinger:    Pathogensis,  Histogensis  u.  Aetiologie  d.  Aneurysmen.  Berl.,  1887. 

50.  Langton  and  Bowlby:    Med.-Chir.  Trans.,  1887.  LXX.  p.  1117. 

(Consult  for  references  to  Ogle.  Wilks,  Holmes,  Church,  Smith,  Good- 
hart,  and  other  previous  literature.) 

51.  Pel  and  Spronck:   Ztschr.  f.  kl.  Med.,  XII,  p.  327. 

52.  Thoma:    Deutsch.  med.  Woch.,  1889,  p.  362. 

53.  Tufnell:    Dubl.  Quart.  Journ.  Med.  Sc,  May,  1853. 

Gexebal  Symptomatology 

54.  Gangolphe  and  Courmont:    Arch.  med.  exper.,  1891,  III,  p.  504. 

55.  Strieker:   Vorles.  iib.  allg.  u.  exper.  Pathologie,  p.  770.    Wiea.  1883. 

Am  Embolism 

56.  Bert:    La  pression  barometrique.  etc.    Paris,  1878. 

57.  Couty:    Etudes  exp§r.  sur  I'entree  de  I'air  dans  les  veines.     ThSse.     Paris, 

1875. 

(Also  for  reference  to  Barthelemy.) 

58.  Feltz:    Compt.  rend.,  1878.  LXXXVI,  No.  5. 

59.  Ewald  and  Robert:    Pfluger's  Arch.,  1883,  XXI.  p.  160. 

60.  Hauer:    Ztschr.  f.  Heilk..  1890,  XI,  p.  159. 

61.  Janeway:    Trans.  Assoc.  Amer.  Physicians,  1898,  XIII.  p.  87. 

62.  Jurgensen:    Deutsch.  Arch.  f.  kl.  Med.,  1882.  XXXI.  p.  441. 

63.  Laborde  and  Muron:    Compt.  rend.  soc.  de  biol.,  1873,  V. 

64.  Lewin:    Arch.  f.  exp.  Path.  u.  Pharm.,  1897,  XL,  p.  308. 

65.  Passet:    Arb.  a.  d.  path.  Inst,  zu  Miinchen,  p.  293.     Stuttg.,  1886. 

66.  Welch  and  Flexner:    .lourn.  Exp.  Med.,  1896.  I,  p.  5. 

67.  Welch  and  Nuttall:    Johns  Hopkins  Hosp.  Bulletin,  1892,  III,  p.  81. 


EMBOLISM  255 

Fat  Embolism 

68.  Beneke:    Ziegler's  Beitr.,  1897,  XXII,  p.  343. 

69.  Hanriot:    Compt.  rend.  acad.  des  sc,  1896,  CXXII,  p.  753;  CXXIII,  p.  833; 

1897,  CXXIV,  pp.  235  and  778. 

70.  Ribbert:    Correspondenz-Bl.  f.  schweiz.  Aerzte,  1894,  XXIV,  p.  457. 

71.  Sanders  and  Hamilton:    Edin.  Med.  Journ.,  1879-80,  XXV,  p.  47. 

72.  Wagner:    Arch.  d.  Heilk.,  1862,  III,  p.  241;  1865,  VI. 

73.  Zenker:    Beitr.  zu  norm.  u.  path.  Anat.  d.  Lunge,  Dresden,  1862 

Embolism  by  Parenchymatous  Cells 

74.  Aschoff:    Virchow's  Arch.,  1893,  CXXXIV,  p.  11. 

75.  Gaylord:    Proc.  Path.  Soc,  Philadelphia,  1898,  N.  S.  I,  p.  184. 

76.  Hanau:    Fortschr.  d.  Med.,  1886,  IV,  p.  387. 

77.  Lubarsch:    Fortschr.  d.  Med.,  1893,  XI,  pp.  805  and  845. 

(Consult  for  references  to  Turner,  Jiirgens,  Klebs,  Schmorl,  Zenker, 
and  Hess.) 

78.  Idem:  Virchow's  Arch.,  1898,  CLI,  p.  546. 

79.  Maximow:   Virchow's  Archiv,  1898,  CLI,  p.  297. 

(Also  for  references  to  Leusden  and  Kassjanow. ) 

80.  Neumann:    Monatsschr.  f.  Geburtsh.  u.  Gynakol.,  1897,  VI,  pp.  17,  157. 

81.  Pick:    Berl.  kl.  Woch.,  1897,  p.  1069. 

(Also  for  Schmorl.) 

82.  Schmidt,  B.:    Centralbl.  f.  allg.  Path.,  1897,  VIII,  p.  860. 

83.  Schmorl:    Centralbl.  f.  Geburtsh.  u.  Gynakol.,  1897,  p.  1216. 

Pulmonary  Embolism 

84.  Bang:    Jattagelser  og  Studier  over  d^delig  Embolie  og  Thrombose  i  Lunge^ 

artierne.     Copenhagen,  1880. 

85.  Biinger:    Ueb.  Embolie  d.  Lungenarterie.    Inaug.-Diss.    Kiel,  1895. 

86.  Cohnheim  and  Litten:    Virchow's  Archiv,  1875,  LXV,  p.  99. 

87.  Freyberger:   Trans.  Path.  Soc.  London,  1898,  XLIX,  p.  27. 

88.  Fujinami:    Virchow's  Archiv,  1898,  CLII,  pp.  61,  193. 

(Also  for  Oestreich.) 

89.  Gluzinski:    Deutsch.  Arch.  f.  kl.  Med.,  1895,  LIV,  p.  178. 

(For  references  to  Perl  and  Lipmann,  Sommerbrodt  and  Nothnagel.) 

90.  Grawitz:    Virchow's  Festschrift  der  Assistenten,  Berlin,  1891. 
90a.  Gsell:    Mittheil.  a.  Klinik  u.  med.  Inst.  d.  Schweiz,  III,  R.  Hft.  3. 

(Also  for  Hanau.) 

91.  Hamilton:    A  Text-Book  of  Pathology,  I,  p.  683.    London,  1889. 

92.  Kiittner:    Virchow's  Archiv,  1878,  LXXIII,  p.  39. 

93.  Klebs:    Allg.  Path.,  II,  p.  20.    Jena,  1889. 

94.  Litten:    Charite-Annalen,  1878,  III,  1876,  p.  180. 

95.  Mogling:    Ziegler's  Beitr.,  1886,  p.  133. 

(See  also  reference  90.) 

96.  Orth:    Centralbl.  f.  allg.  Path.,  1897,  VIII,  p.  859. 

97.  Perl:    Virchow's  Archiv,  1874,  LIX,  p.  39. 

98.  Serre:    De  I'origine  embolique  des  thromboses  de  I'artere  pulmon.     These. 

Lyon.  1895. 


256  EMBOLISM 

99.  Sgambati:    Arch,  ed  atti  d.  soc.  ital.  di  chir.    Roma,  1897,  XI,  p.  37. 

100.  Willgerodt:   Arb.  a.  d.  path.  Inst,  in  Gottingen,  p.  100.    Berlin,  1893. 

101.  Zahn:    Centralbl.  f.  allg.  Path.,  1897,  VIII,  p.  860. 

Splenic  Infabction.    Renal  Infabction 

102.  Ponfick:    Virchow's  Arch.,  1874,  LX,  p.  153. 

103.  Thorel:   Virchow's  Arch.,  1896,  CXLVI,  p.  297. 

104.  Traube:    Gesammelte  Beitr.  zu  Path.  u.  Physiol.,  II,  p.  347.     Berl.,  1871. 

Embolism  and  Thrombosis  of  the  Mesenteric  Arteries 

105.  Beckmann:    Virchow's  Arch.,  1858,  XIII,  p.  501. 

106.  Chiene:    Journ.  Anat.  and  Physiol.,  1869,  III,  p.  65. 

107.  Councilman:    Boston  Med.  and  Surg.  Journ.,  1894,  CXXX,  p.  410. 

108.  Elliot:    Annals  of  Surgery,  1895,  XXI,  p.  9. 

109.  Faber:    Deutches  Arch.  f.  kl.  Med.,  1875,  XVI,  p.  527. 

110.  Finlayson:    Glasgow  Med.  Journ.,  1888,  XXIX,  p.  414. 

111.  Gerhardt:    Wiirzb.  med.  Ztschr.,  1863,  IV,  p.  141. 

112.  Gordon:    Brit.  Med.  Journ.,  1898,  I,  p.  1447. 

113.  Karcher:    Correspondenz-Bl.  f.  schweiz.  Aertze,  1897,  XXVII,  p.  548. 

114.  Kaufmann:    Virchow's  Arch.,  1889,  CXVI,  p.  353. 

115.  Kussmaul:    Wiirzb.  med.  Ztschr.,  1864,  V,  p.  210. 

116.  Lereboullet:   Rec.  de  mem.  de  m6d.,  1875,  XXXI,  p.  417. 

117.  Litten:    Virchow's  Arch.,  1875,  LXIII,  p.  289. 

118.  Idem:   Deutsche  med.  Woch.,  1889,  p.  145. 

119.  Lorenz:   Ztschr.  f.  kl.  Med.,  1891,  XVIII,  p.  493. 

120.  Lycett:    Brit.  Med.  Journ.,  1898,  II,  p.  84. 

121.  Minkowski:    Mitth.  a.  d.  med.  Klin,  zu  Konigsberg,  1888,  p.  59. 

122.  Moos:   Virchow's  Arch.,  1867,  XLI,  p.  58. 

123.  Nothnagel:    Spec.  Path.  u.  Therap.,  XVII,  p.  156.    Wien,  1898. 

124.  Oppolzer:    Allg.  Wien.  med.  Ztg.,  1862,  VII. 

125.  Packard:    Proc.  Path.  Soc.  Philadelphia,  1898,  N.  S.  I,  p.  288. 

126.  Parenski:    Wiener  med.  Jahrb.,  1876,  p.  275. 

127.  Pieper:    Allg.  med.  Centr.-Ztg.,  1865,  p.  493. 

128.  Ponfick:    Virchow's  Arch.,  1870,  L,  p.  623. 

129.  Tangl  and  Harley:    Centralbl.  f.  d.  med.  Wiss.,  1895,  p.  673. 

130.  Tiedemann:    Von  d.  Verengung  u.  Schliessung  d.  Pulsadern  in  Krankheiten. 

Heidelb.  u.  Leipz.,  1843. 

131.  Watson:    Boston  Med.  and  Surg.  Journ.,  1894,  CXXXI,  p.  552. 

132.  Welch  and  Flexner:    Journ.  Exp.  Med.,  1896,  I,  p.  35. 

Embolism  and  Thbombosis  of  the  Thoracic  Aokta 

133.  Armet:    Th^se.    Paris,  1881. 

134.  Chvostek:    Wiener  med.  Blatter,  1881,  p.  1513. 

(Also  for  references  to  Trost,  Carville,  Liittich,  and  Tewat.) 

135.  Bochdalek:    Vrtljschr.  f.  d.  prakt.  Heilk.,  1845,  VIII,  p.  160. 

136.  Bristowe:    Lancet,  1881,  I,  pp.  131  and  166. 

137.  Jaurand:    Progr.  m^d.,  1882,  X,  p.  147. 

138.  Pitt:    Trans.  Path.  Soc.  London,  1889,  XL,  p.  74. 


EMBOLISM  257 

Embolism  and  Thbombosis  of  the  Abdominal  Aorta 

139.  Cammareri:    Morgagni,  1885,  XXVII,  pp.  1,  113. 

140.  Charrier  and  Apert:    Bull.  soc.  anat.  de  Paris,  1896,  5tli  s.,  X,  p.  766. 

141.  Graham:    Med.-Chir.  Transactions.,  1814,  V,  p.  297. 

142.  Heiligenthal:    Deutsch.  med.  Woch.,  1898,  p.  519. 

143.  Meynard:    Etude  sur  I'obliteration  de  I'aorte  abdom.  par  embolie  ou  par 

thrombose.    These.    Paris,  1883. 

(Meynard's  case  is  identical  with  Bari6's  and  du  Castel's.) 

144.  Roussel:    Etudes  sur  les  embolies  de  I'aorte  abdom.     These.     Lyon,  1893. 

(The  cases  of  Barie  and  of  Desnos  reckoned  as  separate  cases  by  Selter 
and  Roussel  are  identical.) 

145.  Selter:    Ueb.  Embolie  d.  Aorta  abdom.     Inaug.-Diss.     Strassburg,  1891. 

(The  references  to  my  additional  twelve  cases  of  embolism  or  throm- 
bosis of  the  abdominal  aorta  are  Nos.  146  to  157  inclusive.) 

146.  Ballingall:    Trans.  Med.  and  Phys.  Soc.  Bombay,  1857,  N.  S.  Ill,  App.  p.  XXV. 

147.  Bristowe:    Trans.  Path.  Soc.  London,  1872,  XXIII,  p.  21. 

148.  Carter:     Trans.   Med.  and  Phys.  Soc.  Bombay    (1859),   1860,  N.  S.  V,  App. 

p.  XXII. 

149.  Goodworth:    Brit.  Med.  Journ.,  1896,  1,  p.  1501. 

150.  Kirkman:    Lancet,  1863,  II,  p.  510. 

151.  Mauz:    Berl.  kl.  Woch.,  1889,  p.  812. 

152.  Nunez:    Gaz.  med.  de  la  Habana,  1879-80,  II,  p.  160. 

153.  Osier:    Trans.  Assoc.  Amer.  Physicians.  1887,  II,  p.  135. 

154.  Pettit:    New  Orleans  Med.  and  Surg.  Journ.,  1880-81,  N.  S.  VIII,  p.  1151. 

155.  Schilling:    Miinch.  med.  Woch.,  1895,  p.  227. 

156.  Scholz:    Ein  Fall  von  Obturation  d.  Aorta  abdom.     Inaug.-Diss.    Tubingen, 

1850. 

157.  Wilbur:    Amer.  Journ.  Med.  Sc,  1857,  N.  S.  XXXIV,  p.  286. 

158.  Barth:    Bull.  Soc.  anat.  de  Paris,  1848,  XXIII,  p.  260. 

159.  Herter:    Journ.  Nerv.  and  Mental  Dis.,  1889,  XIV,  p.  197. 

(For  references  to  Schiffer,  Weil,  Ehrlich  and  Brieger,  and  Spronck.) 

160.  Herxheimer:    Virchow's  Arch.,  1886,  CIV,  p.  20. 

161.  Kadyi:    Ueb.  d.  Blutgefasse  d.  menschl.  Riickenmarkes.    Lemberg,  1889. 

162.  Litten:    Virchow's  Arch.,  1880,  LXXX,  p.  281. 

163.  Popoff:    Arch.  f.  Gynak.,  1894,  XLVII,  p.  12. 

164.  Williamson:    On  the  Relation  of  the  Spinal  Cord  to  the  Distribution  and 

Lesions  of  the  Spinal  Blood- Vessels.    London,  1895. 

Hepatic  Infakction 

165.  Arnold:    Virchow's  Arch.,  1891,  CXXIV,  p.  388. 

166.  Chiari:    Centralbl.  f.  allg  Path.,  1898,  IX,  p.  839. 

167.  Cohnheim  and  Litten:    Virchow's  Arch.,  1876,  LXVII,  p.  153. 

168.  Doyon  and  Dufourt:    Arch,  de  physiol.,  1898,  5th  s.  X,  p.  522. 

169.  Flexner:    Johns  Hopkins  Hosp.  Reports,  1897,  VI,  p.  259. 

170.  Klebs:    Virchow's  Festschrift  der  Assistenten,  1891,  p.  8. 

171.  Kohler:    Arb.  a.  d.  path.  Inst,  in  Gottingen,  1893,  p.  121. 

172.  Lubarsch:    Fortschr.  d.  Med.,  1893,  XI,  p.  809. 

173.  Osier:    Trans.  Assoc.  Amer.  Phys.,  1887,  II,  p.  136. 


258  EMBOLISM 

174.  Pitt:    Brit.  Med.  Journ..  1895.  I,  p.  420. 

175.  Rattone:    Arch,  per  le  sc.  med.,  1888,  XII,  p.  223. 

176.  Welch  and  Flexner:    Johns  Hopkins  Hosp.,  Bulletin,  1892,  III,  p.  17. 

177.  Wooldridge:    Trans.  Path.  Soc.  London,  1888,  XXXIX,  p.  421. 

178.  Zahn:   Centralbl.  f.  allg.  Path.,  1897,  VIII,  p.  860. 

EmBOLIvS.M    of   the   COBOXABT   ABTERIE3 

179.  Chiari:    Prag.  med.  Woch.,  1897,  Nos.  6  and  7. 

180.  Hektoen:    Med.  News,  1892,  LXI,  p.  210. 

181.  Marie:    L'infarctus  du  myocarde,  p.  30.    Paris,  1897. 

182.  Rolleston:    Brit.  Med.  Journ.,  1896,  II.  p.  1566. 

Embolism  and  Thrombosis  of  the  Retinal  Vessbxs 

183.  Fischer:    Ueb.  d.  Embolie  d.  Art.  centr.  retinae.    Leipzig,  1891. 

184.  Kern:    Zur  Embolie  d.  Art.  centr.  retinae.     Inaug.-Diss.    Zurich,  1892. 


VENOUS  THROMBOSIS   IX   CAEDIAC   DISEASE* 

One  of  the  most  interesting  points  of  view  from  which  to  consider  the 
subject  of  thrombosis  is  that  of  its  association  with  different  diseases. 
The  study  of  such  association  not  only  is  of  clinical  interest,  but  is  capable 
of  contributing  to  our  knowledge  of  the  causation  of  thrombosis,  which 
in  many  respects  is  still  obscure.  Infectious  and  chronic  wasting  diseases 
are  those  most  frequently  complicated  or  followed  by  vascular  thrombosis 
of  medical,  as  distinguished  from  surgical,  interest;  typhoid  fever  and 
influenza  heading  the  list  among  the  former,  and  tuberculosis  and  cancer 
among  the  latter.  There  are,  however,  a  number  of  other  diseases  with 
which  peripheral  thrombosis  may  be  associated  more  or  less  frequently, 
and  to  one  of  these  less  generally  recognized  associations  I  wish  to  call 
attention  in  this  paper. 

Although  there  are  scattered  reports  of  a  number  of  instances  of  the 
occurrence  of  venous  thrombosis  in  diseases  of  the  heart,  I  cannot  find 
that  particular  attention  has  been  called  to  this  complication  either  in 
text-books  on  these  diseases  or  in  special  monographs.  This  is  doubtless 
attributable  mainly  to  the  infrequency  of  the  complication,  perhaps  also 
in  part  to  a  failure  to  recognize  it.  By  far  the  largest  number  of  cases 
have  been  reported  by  French  physicians. 

As  will  appear  from  the  following  reports  of  cases,  there  are  certain 
peculiarities  of  the  venous  thrombosis  of  heart  disease  which  render  this 
suject  well  worthy  of  investigation.  For  the  clinical  histories  of  the  eases 
from  the  Johns  Hopkins  Hospital  I  am  indebted  to  my  colleague.  Dr. 
Osier. 

Case  I. — Aortic  and  mitral  insujjiciency.  Adherent  pericardium.  Broken 
compensation.  Thromhosis  of  left  innominate,  jugular,  subclavian,  and 
axillary  veins.  Death. — R.  H.,  negress,  aged  seventeen  years,  admitted  No- 
vember 26,  1898,  died  January  16,  1899,  Nothing  of  importance  in  family 
history  or  in  personal  history,  until  the  occurrence,  six  years  ago,  of  a  severe 
attack  of  inflammatory  rheimiatism,  with  swelling  and  tenderness  of  most 
of  the  joints.  Since  then  she  has  not  been  strong  and  has  had  at  times  rheu- 
matic pains.    In  January,  1898,  occurred  a  second  attack  of  articular  rheu- 

'  After  its  presentation  before  the  Association  of  American  Physicians,  this 
paper  was  published  also  in  the  Festschrift  in  honor  of  Abraham  Jacobi,  M.  D., 
LL.  D.,  New  York,  1900.  I  have  added  to  the  article  in  its  present  form  Case  V, 
which  has  necessitated  changes  in  the  statistical  figures. 

Tr.  Ass.  Am.  Physicians,  Phila.,  1900,  XV,  441-469. 

2.59 


260  VENOUS  THROMBOSIS' 

matism,  since  which  she  has  suffered  from  shortness  of  breath  on  exertion, 
palpitation,  pain  in  the  region  of  the  heart,  and  some  cough.  These  symp- 
toms became  aggravated  during  the  last  two  months. 

Upon  admission,  patient,  who  is  well  nourished,  is  suffering  from  respira- 
tory distress.  No  oedema  of  extremities.  Pulse  112,  somewhat  irregular, 
with  fair  volume  and  tension.  Respirations  40.  Temperature  99.5°  F. 
Large  veins  of  neck  full  and  pulsating.  Marked  bulging  of  pnEcordium,  and 
heaving  impulse  over  heart,  especially  distinct  below  and  outside  of  left 
nipple.  Marked  pulsation  in  episternal  notch.  Point  of  maximum  intensity 
in  sixth  left  interspace,  12  cm.  from  midsternal  line.  Relative  cardiac  dul- 
ness  begins  above  in  left  first  intercostal  space.  Systolic  thrill  at  apex, 
where  on  auscultation  are  heard  intense  musical  systolic  and  rasping  diastolic 
murmurs  transmitted  into  axilla.  In  the  aortic  area  both  sounds  are  re- 
placed by  a  loud  to-and-fro  murmur,  the  diastolic  portion  being  especially 
rough.  Second  pulmonic  sound  intensely  accentuated.  Hearts  action 
irregular  and  violent.     Capillary  pulse  visible. 

At  apex  of  right  lung,  slight  expansion,  dulness,  prolonged,  almost  tubular 
expiration.  A  few  medium-sized  moist  rales  at  base  of  lungs.  No  tubercle 
bacilli  in  sputum. 

Liver  somewhat  enlarged.  Urine  albuminous,  with  hyaline  and  granular 
casts.  Blood  count:  red  corpuscles,  4,524,000;  leucocytes,  12,400;  haemo- 
globin, (i5  per  cent. 

Patient  improved  somewhat  after  admission,  but  her  general  condition 
continued  much  the  same.  The  pulse  at  times  was  ver}'  intermittent,  and 
there  was  much  tenderness  over  the  praecordial  area.  The  temperature  varied 
from  nonnal  to  101°  F. 

January  IJfth.  For  the  first  time  oedema  of  the  left  arm  is  noticed,  most 
marked  around  the  elbow-joint.  The  right  arm  is  free  from  swelling.  The 
face  and  legs  are  moderately  oedematous.  Complains  of  severe  headache. 
Pulse  120,  irregular  and  weak. 

lath.  Q£dema  of  left  arm,  which  is  painful,  has  increased.  Temperature 
100.5°  F.  Pulse  very  intermittent.  Death  occurred  rather  suddenly  at 
G.;JO  p.  m. 

A  ufopsy  by  Dr.  MacCallum,  fourteen  hours  after  death.  Body  of  a  girl, 
rather  slenderly  built,  1()2  cm.  long.  Moderate  oedema  of  ankles  and  feet. 
p]xtensive  a'dema  of  left  arm,  especially  about  the  elbow,  the  hand  being  but 
little  swollen.  No  oedema  of  right  arm  and  no  definite  swelling  of  face  or 
neck. 

About  200  c.  c.  clear  yellowish  fluid  in  peritoneal  cavity.  Surfaces  smooth 
and  glistening.  Praecordial  space  greatly  enlarged,  measuring  16  cm.  trans- 
versely and  10  cm.  vertically.  Firm  adhesions  between  parietal  pericardium 
and  the  pleura,  dia])liragm,  and  other  surrounding  tissues.  Lett  pleural 
cavity  contains  over  300  c.  c.  slightly  turbid,  yellowish  fluid,  the  left  lung 
luirig  much  compressed  by  this  and  the  enlarged  heart.  There  are  many 
easily  torn  plcnral  adhesions.  The  right  pleural  cavity  contains  a  small 
amount  of  fluid  and  ])resents  a  few  light  adhesions. 

The  pericardial  sac  is  obliterated  by  fibrous  adhesions.  The  heart  weighs 
720  grammes,  and  gives  the  following  measurements:  right  ventricle  8  cm. 
long,  its  wall  6  mm.  thick ;  left  ventricle  9^  cm.  long,  its  wall  16  mm.  thick ; 


IN  CARDIAC  DISEASE  2G1 

tricuspid  orifice  10|  em.,  mitral  10  cm.,  aortic  7  cm.  All  of  the  cavities 
much  dilated.  Left  auricle  (^reatly  dilated,  reaching  nearly  to  first  rib. 
Tricuspid  and  pulmonic  valves  delicate.  Mitral  orifice  very  -wide;  valvular 
segments,  particularly  the  posterior,  thickness  and  retracted.  Aortic  valvu- 
lar segments  much  thickened,  stiff,  and  curled  at  their  edges,  so  as  to  be 
markedly  shortened.  No  fresh  vegetations.  Coronary  arteries  patent  and 
free  from  sclerosis.  The  aorta  shows  yellow  streaks  of  fatty  degeneration  of 
the  intima,  and  a  few  small  elevated  patches  of  fresh  sclerosis. 

The  left  innominate  vein,  the  left  internal  and  external  jugular  veins,  the 
left  subclavian  and  axillary  veins  are  occluded  by  a  continuous  fresh  throm- 
bus mass.  The  prevailing  color  of  the  thrombus  is  dark  reddish.  The  part 
occupying  the  innominate  just  before  the  reception  of  the  jugular  vein  and 
that  filling  the  well-developed  bulb  of  the  internal  jugular  vein  is  gray  or 
grayish-red,  firmer  and  more  adherent  to  the  wall,  therefore  older,  tlmn  the 
dark-red,  softer  clot  in  the  distal  portions.  The  thrombus  in  the  jugulars 
stops  somewhat  below  the  level  of  the  larynx.  The  brachial  and  other  veins 
of  the  arm  are  free  from  the  thrombus.  The  tissues  aromid  the  thrombosed 
veins  are  oedematous,  and  freshly  swollen  lymphatic  glands  are  present  in 
their  neighborhood.  The  corresponding  veins  of  the  right  side  are  free  from 
thrombus. 

The  lungs  are  dry,  tousfh,  and  of  a  salmon-pink  color,  evidently  the  seat 
of  chronic  passive  congestion.  The  bronchi  contain  blood-stained  mucus. 
No  areas  of  fresh  consolidation.    Pulmonic  vessels  free  from  thrombi. 

The  liver  is  moderately  enlarged,  and  presents  typical  nutmeg  mottling. 
Spleen  also  enlarged,  firm,  dark  red,  slightly  adherent  to  surrounding  tis- 
sues; Malpighian  bodies  distinct.  Kidneys  swollen,  congested,  the  seat  of 
chronic  passive  congestion.  Gastric  and  intestinal  mucosa  deeply  congested, 
the  solitary  follicles  swollen.    No  important  changes  in  other  organs. 

Microscopical  Examination. — ^The  swollen  lymph  glands  show  marked 
proliferation  of  the  endothelial  cells.  The  heart  muscle  is  slightly  fatty, 
and  shows  scattered  focal  accumulations  of  small  round  cells,  mainly  of  the 
lymphoid  type.  The  kidneys  show  passive  congestion  and  parenchymatous 
degenerations,  without  increase  of  the  connective  tissue.  The  lungs  present 
the  usual  evidences  of  chronic  passive  congestion  of  moderate  degree. 

Sections  of  the  tlirombosed  veins  show  that  the  grayish-red  part  of  the 
thrombus  is  composed  of  platelets,  fibrin,  and  leucocytes  -with  entangled  red 
corpuscles.  A  coral-like  arrangement  of  the  platelet  masses  is  indicated, 
but  is  not  very  distinct.  Leucocytes  are  fairly  numerous.  There  are  no 
evidences  of  organization.  The  intima  and  outer  coats  contain  a  few  leuco- 
cytes, and  the  intima  is  somewhat  swollen,  but  there  are  no  si,gns  of  sclerosis 
or  other  chronic  affection  of  the  veins.  The  redder  parts  of  the  thrombus 
are  richer  in  red  corpuscles,  but  here  also  islands  and  bands  of  platelets  and 
fibrillated  fibrin  are  present.  A  few  chains  of  streptococci  are  detected  in 
sections  stained  by  Gram's  method. 

Bacteriological  Examination  (Dr.  Harris). — Plate  cultures  on  agar  made 
with  all  necessary  precautions  from  the  thrombi  in  the  jugular  veins  showed 
a  considerable  number  of  small,  grayish  colonies,  which  were  demonstrated 
to  be  of  Streptococcus  pyogenes.  No  other  organism  appeared  in  the  cultures. 
Streptococcus  pyogenes  was  cultivated  also  from  the  lungs.    Cultures  from 


262  VENOUS  THROMBOSIS 

tlie  heart's  blood,  (Edematous  tissue  in  left  axilla,  the  spleen  and  other  organs 
were  sterile. 

The  principal  points  of  interest  in  the  preceding  case  are  the  following: 
A  girl,  seventeen  years  old,  with  chronic  aortic  and  mitral  endocarditis 
following  acute  articular  rheumatism,  and  giving  rise  to  insufficiency  of 
both  valves,  with  relative  insufficiency  of  the  tricuspid  valve,  suffered  from  the 
effects  of  broken  compensation.  During  the  last  days  of  life  painful  oedema 
of  the  left  arm  made  its  appearance,  without  implication  of  the  right  arm.  At 
the  autopsy,  in  addition  to  the  advanced  cardiac  lesions  and  their  customary 
secondar}'  effects,  an  infectious  thrombus  was  found  filling  the  innominate, 
subclavian,  axillary,  and  lower  parts  of  the  jugular  vein  on  the  left  side.  The 
oldest  part  of  the  thrombus  occupied  the  lower  bulb  of  the  internal  jugular 
vein  and  the  adjacent  part  of  the  innominate  vein.  The  micro-organism  con- 
cerned was  Streptococcus  pyogenes,  which  was  present  in  the  lungs  and  the 
thrombus,  but  was  not  fomid  elsewhere. 

The  three  following  eases  are  also  from  Dr.  Osier's  service  in  the  Johns 
Hopkins  Hospital : 

Case  II. — Mitral  steriosis.  Thrombosis  of  left  jugular,  axillary,  sub- 
clavian., and  innomin<ite  vevns.  Embolism  of  left  popliteal  artery.  Recovery 
from  effects  of  vascular  occlusion. — E.  0.,  female,  aged  thirty-five  years, 
admitted  January  4,  1899.  History  of  rheumatism  in  family.  Diphtheria 
at  ten,  chorea  at  eleven  years  of  age,  accompanied  by  paralysis  of  the  right 
side.  Since  these  attacks  patient  has  not  been  strong.  No  history  of  scarlet 
fever,  pneumonia,  nor  typhoid  fever.  Obscure  history  of  repeated  attacks 
of  "  rheumatism  "  \nthout  definite  articular  symptoms.  Patient  has  suffered 
for  years  from  shortness  of  breath  on  exertion,  indigestion,  nervousness,  and 
chronic  invalidism.  For  three  weeks  before  admission  has  been  in  bed  with 
epigastric  pain  and  digestive  disturbances. 

Upon  admission  patient  is  very  nervous.  The  point  of  maximum  inten- 
sity of  cardiac  impulse  cannot  be  detected  by  palpation  or  inspection,  but  by 
the  stethoscope  is  located  in  the  fifth  intercostal  space,  10  cm.  from  median 
line.  Area  of  cardiac  dulness  not  much  increased.  Very  distinct  thrill  can 
1)0  felt  at  the  apex,  where  is  heard  a  rough,  intense,  presystolic  murmur  ter- 
minating in  a  short,  sharp  first  sound.  No  second  sound  is  heard  at  the 
apex.  Over  the  l)ody  of  the  heart  the  valvular  sounds  are  distinct  and  snap- 
ping. The  second  pulmonic  sound  is  markedly  accentuated.  Pulse  144, 
small,  irregular  both  in  force  and  rhvthm.  Respiration  .30.  Temperature 
99°  F. 

^fedium-sizod  moist  rales  are  heard  behind,  over  the  lower  parts  of  both 
lungs,  whoro  tliero  is  also  some  impairment  of  resonance. 

The  absolute  hepatic  dulness  extends  from  the  seventh  ril)  to  a  point  5^ 
cm.  ])elow  the  costal  margin  in  tlie  mammary  line.  The  border  of  the  liver 
can  be  distinctly  felt.  There  is  fairly  distinct  pulsation  of  the  liver.  The 
epigaMric  and  right  hypochondriac  regions  are  somewhat  tender  to  pressure. 

There  is  sliglit  (edema  of  Iwth  ankles.  Urine,  sp.  gr.  1017,  contains  a 
pmall  amount  of  albumin  and  hvaline  and  jrranular  casts. 


IN  CAEDIAC  DISEASE  263 

January  12th.    The  left  ankle-joint  is  swollen,  red,  and  tender. 

lyth.  The  left  side  of  the  neck  is  swollen,  and  painful  upon  pressure  or 
movement.    Temperature  100°.    Pulse  124.    Respiration  32. 

20th.  The  fulness  and  tenderness  of  the  left  side  of  the  neck  have  in- 
creased, and  a  sensitive,  cord-like  body  can  be  felt  in  the  course  of  the  in- 
ternal jugular  vein  in  its  lower  part,  indicative  of  thrombosis.  The  pain 
and  swelling  of  the  left  ankle-joint  have  disappeared.  There  are  evidences  of 
partial  consolidation  of  the  right  lung  below  and  behind.  Moist  rales  are 
heard  also  at  the  angle  of  the  left  scapula.    Patient  is  flighty. 

20th.  To-day  appeared  an  oedematous  swelling  of  the  left  arm,  extending 
to  the  hand.  The  left  ann  measures  2  cm.  more  than  the  right  just  above 
the  wrist. 

27th.  The  oedematous,  painful  swelling  is  now  very  marked,  and  occupies 
the  whole  of  the  left  side  of  the  neck,  the  pectoral  region  on  the  left  side, 
the  left  shoulder,  and  the  left  arm  to  the  hand.  The  cedema  has  a  brawny, 
indurated  character,  but  there  is  pitting  on  pressure.  There  is  no  marked 
difference  in  the  superficial  temperature  of  the  two  arms.  The  superficial 
veins  of  the  arm  and  neck  are  distended.  On  account  of  the  oedema  the 
deeper  veins  cannot  be  distinctly  palpated.  Temperature  101°.  Pulse  112. 
Respiration  40. 

31st.    The  swelling  of  the  left  arm  is  less ;  that  of  the  neck  continues. 

February  9th.  A  cord-like  swelling  of  the  left  external  jugular  vein  can 
be  traced  up  to  the  angle  of  the  jaw.    The  axillary  vein  is  likewise  thrombosed. 

2C)th.  The  hard  redema  of  the  left  arm  and  neck  has  continued,  at  times 
lessening  and  then  returning.     There  is  oedema  of  both  lower  extremities. 

March  IGth.  Pain  in  the  left  side  and  a  marked  pleuritic  friction  rub  on 
auscultation. 

Soon  after  this  date  the  general  condition  of  the  patient  improved,  and 
the  ffidema  of  the  arm  and  neck  gradually  disappeared  through  the  establish- 
ment of  a  collateral  circulation. 

On  November  24th  embolism  of  the  left  popliteal  artery  occurred,  char- 
acterized by  loss  of  pulsation  in  left  popliteal  and  tibial  arteries,  sudden  pain, 
numbness,  cyanosis,  and  coldness  of  the  left  foot  and  leg.  The  history  of 
this  embolic  attack  need  not  be  given  in  detail.  Suffice  it  to  say  that  a  col- 
lateral circulation  was  completely  re-established.  The  patient  is  still  in  tlie 
liospital. 

The  diagnosis  made  by  Dr.  Osier  in  this  case  was  mitral  stenosis  with 
thrombosis  of  the  left  innominate,  left  internal  and  external  jugulars,  left 
subclavian,  and  left  axillary  veins.  The  location,  extent,  and  persistence 
of  the  hard,  painful  oedema,  lasting  for  nearly  three  months,  make  prob- 
able the  existence  of  thrombosis  of  the  left  innominate  and  subclavian 
veins,  while  that  of  the  jugulars  and  axillary  vein  was  definitely  recognized. 
The  history  indicates  that  the  thrombosis  started  in  the  lower  part  of  the 
internal  jugular  vein.  It  is  to  be  noted  that  the  onset  of  the  thrombosis 
was  preceded  for  a  few  days  by  a  red,  painful  swelling  of  the  left  ankle- 
joint,  and  was  accompanied  by  evidences  of  acute  pneumonia  and  by  ele- 


364  YEXOUS  THROMBOSIS' 

vation  of  temperature,  also  that  during  its  course  acute  pleurisy  appeared. 
There  is,  therefore,  much  probability  in  the  supposition  that  the  thrombus 
in  this  case,  as  in  the  preceding,  was  of  infectious  nature. 

Case  III. — Mitral  and  aortic  insufficienci/ ;  general  anasarca;  thrombosis 
of  the  left  axillary  and  brachial  veins.  Death. — H.  M.,  aged  sixteen  years, 
admitted  February  24,  1900;  died  March  8th.  No  history  of  infectious 
disease  except  pneumonia  at  seven  years  of  age.  Present  illness  began  in 
August,  1899,  with  vomiting  and  indigestion.  Says  that  he  had  rheumatism 
in  September,  but  no  definite  history  of  affection  of  joints  was  obtained.  Re- 
peated attacks  of  gastric  pain  and  vomiting  during  the  autumn.  In  January, 
feet,  legs,  and  abdomen  became  swollen,  and  he  was  confined  to  bed.  Tiie 
dropsy  increased,  and  a  week  ago  the  face  and  hands  began  to  swell.  Con- 
tinued shortness  of  breath;  digestive  disturbance  continued. 

Examination  on  Admission. — Patient  is  propped  up  in  bed;  respiration 
32,  somewhat  labored,  and  irregular.  Cyanosis  of  face  and  extremities ; 
oedema  of  face,  thorax,  upper  and  lower  extremities,  penis,  and  scrotum ; 
marked  oedema  of  left  forearm  and  hands;  ascites.  Pulse  124,  regular  in 
force  and  rhythm,  fair  volume,  low  tension,  hyperdicrotic ;  pulsation  of 
cervical  veins. 

Distinct  praecordial  bulging  and  general  heaving  in  this  region.  Apex* 
beat  in  fifth  interspace  11  cm.  to  left  of  median  line;  area  of  cardiac  dulnes3 
increased,  extending  1  cm.  to  right  of  sternum  and  upward  to  left  second  rib. 
At  apex  first  sound  replaced  by  loud  systolic  murmur  heard  far  out  in  axilla; 
second  sound  faint.  In  aortic  area  both  sounds  enfeebled,  the  second  sound 
being  accompanied  by  a  faint  diastolic  murmur  traceable  dovm  along  right 
border  of  sternum ;  second  pulmonic  sound  distinctly  accentuated. 

Physical  signs  of  a  moderate  amount  of  fluid  in  left  pleural  cavity  are 
present,  also  some  dulness  and  impairment  of  respiratory  and  vocal  sounds 
on  right  side  below  and  beliind,  with  a  few  fine  moist  rales. 

Absolute  hepatic  dulness  begins  at  sixth  rib  and  is  continuous  with  the 
abdominal  flatness  due  to  ascites,  which  is  marked. 

The  oedema  of  the  left  arm  and  hand  is  so  much  greater  than  that  of  the 
right  arm  that  thrombosis  was  suspected.  Upon  palpation  the  left  axillary 
and  brachial  veins  can  be  distinctly  felt  as  hard,  swollen,  somewhat  sensitive, 
cord-like  cylinders,  which  can  be  made  to  roll  beneath  the  finger. 

Blood  Cottnts.— lied  blood-corpuscles,  6,900,000;  leucocytes,  14,600; 
haemoglobin,  76  per  cent;  86  per  cent  of  the  leucocytes  are  poh-morphonu- 
clear.  Urine  contains  a  small  amount  of  albumin  and  some  hyaline  casts; 
specific  gravity,  1027. 

After  admission  the  oedema  of  the  left  arm  and  hand  continued  to  increase 
and  reached  an  extreme  degree,  so  that  splits  appeared  in  the  corium.  The 
superficial  veins  were  distended.  Temperature  most  of  the  time  a  little  below 
normal,  only  occasionally  rising  to  99°  and  once  to  100°  F. 

March  1st.  Jaundice  appeared.  The  next  day  a  hemorrhagic  eruption 
appeared  over  the  abdomen.  Chcync-Stokes  breathing  set  in,  the  sputum 
became  tinged  with  blood,  and  death  occurred  March  8th.  Unfortunately, 
permission  could  not  be  obtained  for  an  autopsy. 


IN  CAEDIAC  DISEASE  265 

In  the  pret'eding  case  of  uncompensated  mitral  regurgitation  the  general 
dropsy  was  so  great  that  only  the  excess  of  ocderaatous  swelling  of  the  left 
arm  led  to  examination  for  venous  thrombosis,  of  which  positive  evidences 
were  found  in  the  left  brachial  and  axillary  veins.  Whether  other  veins 
were  also  implicated  could  not  be  determined,  as  no  autopsy  was  permitted. 

Case  IV. — Mitral  insufficiency ;  thrombosis  of  left  femoral  vein;  recovery 
from  effects  of  thromhosis. — M.  H.,  male,  aged  seventy-eight  years'  admitted 
December  27,  1898;  discharged  January  10,  1899.  Patient  had  been  in 
hospital  a  year  ago,  suffering  from  abdominal  pain  and  constipation.  At  this 
time  mitral  insufficiency  was  recognized.  No  history  of  rheumatism  or  of 
other  infectious  disease,  except  measles  and  smallpox  in  childhood.  Has 
suffered  of  late  years  from  pain  in  the  abdomen,  constipation,  bronchitis, 
and  increased  frequency  of  urination. 

Three  days  before  admission  was  seized  with  pain  on  the  inner  side  of  left 
ankle  and  inside  of  upper  part  of  thigh,  soon  followed  by  swelling  of  the  left 
leg  and  about  the  ankle. 

On  admission  a  rough  systolic  murmur  is  heard  at  the  apex,  transmitted  to 
the  axilla,  and  heard  also  over  the  body  of  the  heart.  Systolic  whiff  over 
aortic  and  pulmonic  areas.  Point  of  maximum  intensity  of  cardiac  impulse 
in  fifth  intercostal  space  11  cm.  to  left  of  median  line.  Veins  of  neck  full 
and  heaving,  but  M'ithout  distinct  pulsation.  Superficial  veins  of  nose  and 
cheeks  dilated ;  physical  signs  of  emphysema  and  bronchitis.  Pulse  96, 
regular ;  respirations  20.    Radial  and  temporal  arteries  tortuous  and  sclerotic. 

The  left  lower  extremity  cedematous  from  the  groin  to  the  foot,  the  swell- 
ing being  most  marked  around  the  ankle.  Superficial  temperature  of 
left  leg  somewhat  higher  than  that  of  right;  superficial  veins  dilated.  An 
indurated,  sensitive  cord  can  be  felt  in  the  left  Scarpa's  triangle,  running 
obliquely  doTvaiward  and  inward.  The  deep  lymphatic  glands  below  Pou- 
part's  ligament  on  the  left  side  are  somewhat  enlarged.  The  pulsation  of  the 
left  femoral  arter}-  is  less  distinct  than  that  of  the  right ;  slight  oedema  of  the 
right  leg. 

Blood  Count. — Eed  blood-corpuscles,  3,800,000 ;  leucocytes,  5000  ;  haemo- 
globin, 40  per  cent.  Temperature  remained  about  normal,  occasionally  ris- 
ing in  the  evening  to  a  little  over  99°  F.  Urine :  specific  gravity,  1020 ;  acid, 
faint  traces  of  albumin  ;  no  casts. 

The  cedema  of  the  left  leg  gradually  lessened,  and  on  January  10th  patient 
was  discharged  at  his  request  with  only  a  little  oedema  of  the  extremities. 

In  the  foreofoinrr  case  there  were  no  marked  evidences  of  disturbed  com- 
pensation  of  the  mitral  lesion,  and  there  was  arterial  sclerosis.  The  rela- 
tionship of  the  venous  thrombosis  to  the  cardiac  lesion  was  not,  therefore, 
so  evident  as  in  the  three  cases  first  reported,  and  probably  this  case  does 
not  properly  belong  in  the  same  category. 

For  the  notes  of  the  following  typical,  unpublished  case,  occurring  in 
the  service  of  Dr.  James  B.  Herrick,  at  the  Cook  County  Hospital,  Chicago, 
I  am  indebted  to  the  kindness  of  Dr.  H.  Gideon  Wells,  who,  when  interne 
at  the  hospital,  observed  the  patient: 
20 


266  VENOUS  THROMBOSIS 

Case  V. — Arteriosclerosis ;  mitral  and  tricuspid  insuffici-ency ;  fibrous 
myocarditis  and  fatty  heart;  general  anasarca;  chronic  interstitial  nephritis; 
thrombosis  of  left  internal  jugular,  subclavian,  ancillary,  and  brachial  veins. 
Death. — J.  C,  negro,  aged  fifty-three  years,  admitted  January  10,  1898 ;  died 
July  24,  1898.  History  of  an  old  syphilitic  infection  and  of  excessive  use 
of  alcohol.  Patient  stated  that  for  three  weeks  preceding  admission  he  had 
suffered  from  pain  in  the  chest,  cough,  increasing  difficulty  in  respiration, 
and  swelling  of  the  legs  and  ankles,  later  of  the  face,  ■with  increased  fre- 
quency of  urination. 

Examination  showed  very  marked  general  anasarca,  with  slight  hydro- 
peritoneum  and  extensive  hydrotliorax.  The  cardiac  dulness  extended  2  cm. 
to  the  right  of  the  sternum,  and  11  cm.  to  the  left  of  the  sternal  lK)rder;  the 
base  reached  to  the  level  of  the  second  costal  cartilage.  There  was  a  mitral 
regurgitant  murmur.  The  arteries  were  hard  and  tortuous ;  the  pulse  in  the 
radial  and  carotid  arteries  almost  imjx^rceptible.  Hepatic  dulness  extended 
a  short  distance  below  the  costal  margin;  the  s{)leen  could  not  be  ])alpat€d. 

The  patient  remained  in  tbe  hospital  until  his  death,  six  and  a  half  montbs 
after  entrance.  During  this  time  he  was  generally  bedridden  and  suffered 
from  severe  dyspnoea,  occasional  attacks  of  praxordial  pain,  and  extensive, 
general  anasarca.  The  urine  was  loaded  with  allmmin  and  contained  large 
numbers  of  casts.  At  times  the  amount  of  fluid  in  the  pleural  cavities  was 
so  large  as  to  require  paracentesis. 

About  a  month  before  death  it  was  noticed  that  the  left  arm  was  much 
more  cedematous  than  the  right,  although  there  was  more  than  a  moderate 
amount  of  fluid  in  the  latter.  This  condition  was  observed  accidentally, 
being  apparently  of  gradual  development,  and  the  patient  experienced  no 
pain  referable  to  this  trouble.  The  oedema  remained  little  changed  until  the 
time  of  death,  which  was  the  outcome  of  a  gradual  cardiac  exhaustion. 

Autopsy  (Dr.  S.  M.  White). — Body  well  nourished.  Oedema  of  all  parts 
of  the  body,  most  marked  in  the  left  upper  extremity,  penis,  and  scrotum. 
Ulcer,  size  of  a  dime,  covered  by  a  gray,  false  membrane,  on  tbe  left  leg. 

Alx)ut  four  litres  of  bloody,  serous  fluid  in  tlie  peritoneal  cavity,  tbe  walls 
of  which  are  thick,  wliite,  and  fibrous.  The  left  pleural  cavity  contains  al)0ut 
one  litre  of  clear  serum,  with  flakes  of  fibrin ;  the  right  a  somewhat  smaller 
quantity.  A  few  fibrous  adhesions  at  apices.  The  pericardial  sac  contains 
about  ]00  c.  c.  of  serous  fluid;  a  few  fibrous  adhesions  bind  tlie  loft  auricle 
to  the  aorta. 

Lower  lobe  of  the  left  lung  carnified  from  pressure;  general  pulmonary 
cedema;  ha?morrhagic  infarction  in  right  lobe.  Healed  tuberculous  nodules 
in  the  apices  and  the  peribronchial  lymphatic  glands. 

Coronary  arteries  dilated  and  atlieromatous.  I?ioht  auricle  reaches  4  cm. 
to  the  right  of  the  median  line.  Kight  ventricle  contains  a  large,  adherent, 
grayish,  ante-mortem  thrombus.  The  tricuspid  orifice  much  dilated.  The 
cavity  of  left  ventricle  measures  8.")  cm.  in  length,  its  walls  1.5  to  2  cm.  in 
thickness;  that  of  the  right  ventricle  9.5  cm.  in  length,  its  walls  5  to  6  mra. 
in  thickness.  Aortic  valves  normal,  save  for  a  few  yellowish  tiiickenings  at 
the  bases.  Mitral  segment'',  thickened,  retract<?d ;  the  orifice  wider  than 
normal.  Endocardium  everywhere  somewhat  thickened.  Papillary  muscles 
mottled  with  yellowish  dots  and  streaks.     Myocardium  firm,  brownish-yel- 


IN  CAEDIAC  DISEASE  2G7 

low,  and  contains  many  grayisli-white  fibrous  areas  and  streaks.  Arteries 
atheromatous,  especially  the  aorta  at  its  beginning  and  at  the  origin  of  the 
thoracic  branches. 

The  left  subclavian  vein  is  filled  with  a  mixed  adherent  thrombus,  in  places 
grayish,  but  predominately  brownish-black,  which  occupies  also  the  axillary 
and  brachial  veins  to  the  middle  of  the  arm.  At  the  beginning  of  the  left 
subclavian  vein  is  a  yellowish,  raised,  sclerotic  area,  about  the  size  of  a  bean, 
to  which  the  clot,  which  here  seems  to  be  channelled,  is  firmly  adherent. 
There  is  also  a  thrombus  of  a  brownish-yellow  color  in  the  lower  end  of  the 
internal  jugular  vein,  around  which  tlie  lymphatic  glands  are  somewhat 
enlarged  and  pigmented. 

Spleen  somewhat  enlarged,  dark-red,  firm.  Typical  nutmeg  liver.  Kid- 
neys are  the  seat  of  typical  arterio-sclerotic  nephritis,  with  adherent  capsule, 
irregular  surface,  thinned  cortex  and  obscure  markings.  Other  organs  and 
tissues  normal. 

Microscopical  examination  of  the  thrombus  in  the  subclavian  vein  showed 
it  to  be  composed  of  platelets,  filjrin,  and  blood-corpuscles,  with  a  con- 
siderable amount  of  connective  tissue  grooving  into  it. 

In  the  foregoing  case  the  cardiac  affection  was  associated  with  arterio- 
sclerosis and  advanced  chronic  interstitial  nephritis,  the  patient  being  fifty- 
three  years  of  age.  The  excess  of  oedema  of  the  left  arm  over  that  of  the  riglit 
attracted  attention  a  month  before  death,  but  it  was  unattended  by  pain 
or  other  symptoms.  The  thrombus  apparently  started  from  a  sclerotic  patch 
in  the  left  subclavian  vein  and  was  undergoing  organization  at  the  time 
of  death. 

Thrombosis  of  pulmonary  vessels,  which  is  not  particularly  uncommon 
in  uncompensated  cardiac  disease,  is  of  course  not  to  be  included  in  the  same 
class  as  peripheral  venous  thrombosis.  I  have  also  excluded  from  considera- 
tion the  venous  thromboses  complicating  general  arterio-sclerosis  and  chronic 
nephritis,  even  when  associated  with  cardiac  hypertrophy  and  dilatation, 
unless,  as  in  Case  V.,  the  symptoms  are  clearly  referable  to  cardiac  disease. 
Our  autopsy  records  contain  five  cases  of  thrombosis  of  the  femoral  and 
iliac  veins  complicating  arterio-sclerosis  and  chronic  nephritis  accompanied 
by  cardiac  hypertrophy.  In  two  of  these  there  was  atheroma  of  the  aortic 
valves,  with  some  insufficiency.  There  is  one  instance  of  thrombosis  of 
the  superior  mesenteric  veins  associated  with  small  kidneys  and  cardiac 
hypertrophy.  A  case  of  thrombosis  of  the  iliac  and  femoral  veins  on  both 
sides,  associated  with  pulmonary  emphysema  and  hypertrophy  and  dilata- 
tion of  the  right  side  of  the  heart,  has  also  been  omitted  as  not  falling  under 
the  class  considered  in  this  article.  For  the  same  reason  I  have  omitted 
a  case  in  our  records  of  thrombosis  of  the  right  femoral  vein  complicating 
cirrhosis  of  the  liver  with  sclerosis,  calcification,  and  insufficiency  of  the 
aortic  valves,  and  also  instances  of  thrombi  in  varicose  veins  in  cases  of  heart 
disease. 


268  VENOUS  THROMBOSIS' 

The  arterial  thromboses  complicating  cardiac  diseases  are  of  much  inter- 
est. Doubtless  most  of  those  in  the  systemic  arteries  are  of  embolic  origin, 
but  there  is  evidence  that  some,  particularly  in  cases  of  extreme  mitral 
stenosis,  are  autochthonous.  This  subject,  to  which  I  have  given  some 
attention  in  my  article  on  "  Thrombosis  and  Embolism "  in  AUbutt's 
"  System  of  Medicine,''  does  not  fall  within  the  scope  of  the  present  paper. 

The  only  attempts,  which  I  have  been  able  to  find,  to  collect  from  the 
records  cases  of  peripheral  venous  thrombosis  complicating  diseases  of  the 
heart  are  those  by  Parmentier  (1889),'  by  Hirschlaff  (18;)3),  and  by  Kahn 
(1896).  Parmentier  and  Kahn  each  report  a  single  case  from  Hanot's 
clinic,  and  refer  to  four  others  which  they  say  are  the  only  ones  they  can 
find  in  French  literature.  Hirschlaff  adds  to  Parmentier's  list  two  per- 
sonal observations  and  the  two  cases  of  Eobert  (1880)  and  of  Ormerod 
(1889).  Peter,  in  1873,  in  his  "  Lecons  de  clinique  medicale,"  reports 
a  case  and  devotes  a  part  of  one  chapter  to  an  interesting  consideration  of 
venous  thrombosis  in  diseases  of  the  heart  without  adding  further  obser- 
vations. Huchard's  article  (1897),  "  Cachexie  cardiaque  et  thomboses 
veineuses,"  and  Helen  Baldwin's  report  of  a  typical  case  (1897),  the  only 
one  which  I  have  met  in  American  literature,  deserve  especial  mention. 
Without  pretence  to  completeness  I  have  been  able  to  collect  reports  of 
twenty-three  cases  to  be  added  to  the  five  observations  already  described. 
I  have  little  doubt  that  a  more  diligent  search  would  bring  to  light  other 
reported  cases.  I  shall  present  in  chronological  order  abstracts  of  these 
twenty-three  cases,  of  some  of  which  the  histories  are  very  meagre. 

Cask  YI. — Bouchut  (1845).  Woman  with  heart  disease  succumbed  to 
obliteration  of  the  deep  and  superficial  veins  of  the  left  leg.  No  further 
details. 

Case  VII. — Bouchut  (1845).  Man  with  heart  disease,  in  whom  occurred 
obliteration  of  the  sujxirior  vena  cava,  jugular,  axillary,  and  deep  arm  veins. 
Engorged,  painful,  hard,  venous  cords  could  be  felt  in  neck  and  arms.  Cya- 
nosis aiid  a'dema  of  face,  neck,  and  arms.  Innumerable  varicose,  agglomer- 
ated, large  veins  appeared  in  neck  and  over  thorax,  A  satisfactor}-  collateral 
circulation  developed,  and  the  man  left  the  hospital  free  from  cyanosis  and 
oedema. 

Case  VIII. — Colin  (1860).  Woman,  sixty-one  years  old.  Stenosis  and 
insufficiency  of  aortic  valves,  some  thickening  of  mitral  segments,  cardiac 
hypertrophy,  and  sjTiiptoms  of  non-compensation.  For  fourteen  weeks 
oedema  of  left  foot  and  leg,  later  also  of  right  foot,  but  here  less  marked. 
At  autopsy,  adherent  old  tlirombi  in  both  iliac  veins,  extending  on  the  left 
side  half-way  down  the  thigh,  and  into  some  of  the  larger  tribubiries  of  the 
femoral  vein,     f  Colin  reports  two  other  cases  of  thrombosis  of  veins  of  the 

'  The  references  will  be  found  at  the  end  of  this  article. 


m  CAEDIAC  DISEASE  269 

lower  extremities  with  cardiac  disease,  but  in  these  there  was  general  arterial 
sclerosis  and  no  pronounced  valvular  lesion.] 

Case  IX. — Jolly  (1860).  Woman  with  organic  disease  of  the  heart  had 
phlegmasia  alba  dolens  of  both  upper  extremities.  Death  occurred  from  an 
ulcero-membranous  affection  of  the  intestine.    No  further  details. 

Case  X. — Ramirez  (1867).  Boy,  aged  twelve  years.  Acute  articular 
rheumatism  one  year  before  admission.  Aortic  and  mitral  insufficiency, 
general  anasarca,  dyspnoea,  and  other  symptoms  of  extreme  cardiac  incom- 
petence. Bloody  expectoration.  Thrombosis  of  jugular,  axillary,  and  sub- 
clavian veins  on  the  right  side.  The  obliterated  external  jugular  vein  very 
evident.  Painful  cedema  of  right  side  of  neck  and  right  arm.  Death  in  coma. 
No  autopsy. 

Case  XI. — Ramirez  (1867).  Man,  aged  fifty  years.  For  six  months  fol- 
lowing intermittent  fever,  dyspnoea,  general  oedema.  Incompletely  compen- 
sated aortic  and  mitral  insufficiency.  CEdema  of  lower  extremities  almost 
disappeared,  while  that  of  face  and  upper  extremities  persisted.  Dyspnoea 
increased.  Painful,  hard  oedema  of  left  arm  and  left  side  of  neck  appeared, 
and  two  large,  hard,  sensitive  cords,  formed  by  the  obliterated  jugular  veins, 
could  be  felt. 

Autopsy  showed  thickening  and  retraction  of  aortic  valves,  with  relative 
mitral  insufficiency.  Great  dilatation  of  all  cardiac  cavities.  Blackish,  firm 
thrombi  in  left  internal  and  external  jugular,  subclavian,  and  axillary  veins. 

Case  XII. — Duguet  (1872).  Patient,  who  formerly  had  acute  articular 
rheumatism,  was  admitted  for  dyspnoea,  cyanosis,  palpitations,  and  cedema 
of  lower  extremities.  Three  days  before  death  there  appeared  painful,  hard 
oedema  of  left  arm,  and  the  axillary  vein  was  felt  as  hard  as  a  cord.  Autopsy 
showed  marked  stenosis,  with  insufficiency  of  the  mitral  orifice,  without  fresh 
endocarditis,  with  cardiac  hypertrophy  and  dilatation,  hydrothorax  and 
hydropericardium,  pulmonary  infarcts,  and  grayish-black,  non-adherent 
thrombi  filling  the  left  subclavian,  a:xillary,  and  brachial  veins. 

Case  XIII. — Peter  (1873).  Woman  with  mitral  insufficiency  and  ob- 
struction, and  with  relative  insufficiency  of  the  tricuspid  valve,  suffered  from 
oedema  of  Tower  extremities,  ascites,  dyspnoea,  cyanosis,  and  great  congestion 
of  lungs  and  liver.  For  past  ten  days  left  arm  cedematous  throughout,  with 
tenderness  at  certain  points;  later  outer  and  lower  part  of  neck  became 
swollen  and  painful,  first  near  the  jimction  of  jugular  and  subclavian  veins. 
The  obliterated  subclavian  [axillary?]  and  external  jugular  veins  could  be 
felt  as  hard,  cylindrical  cords.  Venous  pulse,  formerly  present  in  cervical 
veins  of  both  sides,  is  now  evident  only  on  the  right  side.  The  left  radial 
pulse  is  almost  imperceptible  from  pressure  of  thrombosed  veins  on  the 
arteries.  At  the  end  of  three  weeks  collateral  circulation  was  established 
and  oedema  of  arm  had  disappeared.  General  condition  otherwise  unim- 
proved. 

Case  XIV. — Robert  (1880).  Woman,  age  between  thirty  and  forty  years, 
suffered  for  eight  years  with  cardiac  symptoms  following  pneumonia,  of 
late  palpitation,  dyspnoea,  cyanosis,  oedema  of  lower  extremities  and  ab- 
dominal wall,  moderate  ascites,  pulsation  of  veins  of  neck,  bronchitis,  and 


270  VENOUS  THROMBOSIS' 

pulmonary  congestion.  Mitral  stenosis  and  relative  tricuspid  insufficiency 
dia<,mosed.  For  over  a  month  before  death  patient  had  increasing  oedema 
of  left  arm  (right  being  free)  and  slight  tumefaction  of  left  side  of  face. 
Left  internal  jugular  vein  felt  as  hard  cord ;  veins  over  left  pectoral  region 
becjune  distended. 

Autopsj/. — Extreme  mitral  stenosis,  with  hypertrophy  and  dilatation  of 
the  right  heart,  double  hydrotliorax,  pulmonary  infarcts.  Thrombosis  of  left 
innominate,  subclavian,  and  both  jugular  veins.  The  left  innominate  was 
notably  narrowed  at  confluence  of  jugular  and  subclavian  veins,  and  here 
and  in  the  lower  end  of  the  jugular  was  a  firm,  fibroid,  adherent  thrombus, 
evidently  the  oldest  part  of  the  clot.  The  thrombus  elsewhere  was  in  places 
centrally  softened.  The  walls  of  the  left  subclavian  vein  were  thickened. 
The  clot  in  the  jugular  could  be  traced  to  the  entrance  of  the  linguo-facial 
trunk.  Lymphatic  glajids  in  the  neighborhood  of  the  thrombosed  veins  are 
enlarged.     Superior  vena  cava  free. 

Case  XV. — Parmentier  (from  Hanot's  clinic)  (1889).  Woman,  aged 
forty  years.  For  four  years,  following  puerperal  infection,  cardiac  symp- 
toms; for  last  five  months,  palpitation,  dyspna?a,  cough,  oedema  of  lower 
extremities  ;  and  for  three  weeks  before  admission  painful  oedema  of  left  arm 
and  corresponding  mammary  region;  later,  slight  oedema  of  right  arm. 
Upon  admission:  very  rapid,  irregular  heart  action;  irregular,  small,  inter- 
mittent pulse ;  marked  venous  pulsation  from  systolic  reflux,  intense  dyspnrea, 
pulmonary  rales,  and  albuminuria.  The  left  upper  extremity  is  tumefied 
tbroughoiit  its  whole  extent  by  a  hard,  tender  oedema,  which  extends  also  to 
the  left  mammary  region.  Symptoms  increased  in  gravity  and  death  oc- 
curred four  days  after  admission. 

Autopsy. — Extreme  mitral  insufficiency  and  dilatation  of  all  cavities  of 
the  heart,  left  hydrothorax,  ascites,  nutmeg  liver.  I^eft  sulK-lavian  vein  and 
small  communicating  veins  completely  obliterated  by  a  reddish  thrombus, 
grayish  and  most  adherent  in  the  middle  of  the  vein,  where  it  is  evidently 
oldest,  and  where  there  is  partial  organization.  Upon  micros<'0])ical  exam- 
ination the  coats  of  the  veins  were  found  thickened  and  the  capillaries  in  the 
outer  coats  dilated.  The  jugular  veins  were  free,  and  no  thrombus  was 
found  in  other  veins  of  the  extremities. 

Case  XVL — Ormerod  (1889).  Patient  was  admitted  for  mitral  stenosis. 
At  autopsy  was  found  complete  obstruction  by  adherent  clot  of  both  innom- 
inate veins,  internal  jugulars,  subclavians,  anterior  and  external  jugulars, 
the  clot  being  firmer  on  right  than  left  side.  A  projecting  end  of  clot  hung 
into  superior  cava,  but  was  not  adherent  there,  and  ceased  at  the  opening  of 
tlie  azygos.  Left  auricle  and  right  cavities  of  heart  much  dilated.  The 
sym])toms  of  thrombosis,  which  developed  in  the  hospital,  pointed  to  its  com- 
mencement in  right  subclavian  vein.  No  local  cause  for  it  could  be  found. 
Specimens  were  presented  before  the  London  Pathological  Society  and  no 
further  details  are  given. 

Case  XVIL— Hirschlafr  (from  Leyden's  clinic)  (1893).  Woman.  Re- 
peated attacks  during  last  ten  years  of  articular  rheumatism.  Cardiac 
symptoms  existed  for  stnnt^  timo  before  admission.  Upon  admission,  resy)i ra- 
tions hurried  and  labored,  u'dema  of  lower  extremities,  ascites,  moist  pul- 


m  CARDIAC  DISEASE  271 

monary  rales  behind  and  below,  heart's  action  violent,  with  diffuse  praecordial 
heaving,  cardiac  dulness  much  increased  in  all  directions,  loud  systolic  and 
diastolic  munnurs  at  apex,  feebler  systolic  murmur,  with  indistinct  diastolic 
sound  in  aortic  area,  distinctly  visible  venous  pulsation;  pulse  120,  of  low 
tension;  enlargement  of  liver  and  spleen,  moderate  albuminuria,  diminished 
excretion  of  urine.  No  material  improvement  followed.  Both  hands  be- 
came cedematous.  Six  days  before  death  there  appeared  oedema  of  the  left 
half  of  the  thorax,  reaching  the  middle  line,  and  also  of  the  left  supra- 
clavicular fossa;  later  ccdema  of  left  half  of  face.  Pulsation  disappeared 
from  the  left  external  jugular,  while  it  persisted  in  the  riglit.  A  painful 
hard  cord  could  be  felt  in  the  left  supraclavicular  fossa,  extending  upward 
along  the  course  of  the  external  jugular  vein,  and  a  similar  one  along  that 
of  the  internal  jugular.  Erysipelas  of  the  right  leg  set  in  after  insertion  of 
Ziehl's  needles  to  relieve  the  cedema,  and  patient  died  in  collapse. 

Autopsy. — Extreme  stenosis  and  marked  insufficiency  of  the  mitral  valve 
and  slighter  insufficiency  of  the  aortic  valve ;  cavities  much  dilated.  Throm- 
bosis of  the  entire  left  innominate,  internal  jugular  and  smaller  tributaries, 
external  jugular,  sulx?lavian,  and  axillary  veins.  The  thrombus  is  reddish- 
3'ellow  and  oldest  in  the  jugular  bulb.  The  veins  of  the  upper  arm  contained 
fluid  blood ;  cerebral  sinuses  free ;  red  induration  of  both  lungs ;  small  quan- 
tities of  fluid  in  both  pleural  cavities ;  fresh  hyperplasia  of  spleen. 

Case  XVIII. — Hirschlaff  (1893).  Woman,  aged  fifty-one  years.  Diph- 
theria at  eighteen ;  articular  rheumatism,  without  evident  sequels,  at  twenty 
years  of  age.  For  past  twenty  years  epilepsy  with  periodical  swelling  of  both 
legs,  lasting  for  months  ;  for  last  two  years  persistent  oedema  of  the  legs,  and 
for  a  month  before  admission  palpitation  and  dyspnoea.  Shortly  before 
admission  increasing  painful  swelling  of  left  side  of  neck  and  left  arm.  On 
admission,  marked  cedema  of  lower  extremities  and  of  the  left  side  of  neck 
and  left  arm,  slight  ascites,  slight  cyanosis  and  icterus,  systolic  pulsation  of 
left  external  jugular,  enlargement  of  heart,  heaving  impulse  and  thrill  at 
apex,  loud  murmur  filling  entire  period  before  systole  at  apex,  diastolic 
murmur  in  aortic  area,  dulness  and  creditant  rales  over  posterior,  lower 
chest;  urine  diminished,  concentrated  and  slightly  albuminous;  pulse  108, 
small,  irregular.  The  veins  in  the  left  side  of  neck  and  over  shoulder  became 
much  distended  and  the  cedema  increased  in  extent.  Three  weeks  later  the 
right  side  of  the  neck  and  thorax,  and  then  the  face,  became  cedematous. 
Pulmonary  symptoms.  Repeated  epileptic  attacks  occurred,  accompanied 
and  followed  by  extreme  cyanosis  and  dyspnoea.  In  one  of  these  death  ensued 
a  month  after  admission. 

Autopsy. — Cardiac  hyperthrophy,  extreme  dilatation  of  right  ventricle  and 
auricles;  tricuspid  valve  thickened,  its  chordae  shortened  and  gro\\Ti  together ; 
extreme  stenosis  of  mitral  orifice,  insufficiency  of  aortic  valves,  on  which  are 
fresh  vegetations ;  myocardium  flabby,  pale,  and  yellow.  IModerato  accumu- 
lation of  fluid  in  pleural  and  pericardial  cavities ;  recent  and  old  pulmonary 
infarcts;  chronic  passive  congestion  of  liver,  spleen,  and  kidneys.  Throm- 
bosis of  superior  vena  cava,  left  innominate  vein,  left  subclavian  and  both 
internal  jugular  veins.  The  oldest  part  of  the  thrombus  occupies  the  bulb 
of  the  left  jugular,  where  it  is  firm,  closely  adherent,  and  ])artly  organized. 
Tissues  around  thrombosed  veins  behind  manubrium  sterni  cedematous. 
Small  thrombus  in  the  left  lateral  sinus  of  the  dura  mater. 


272  VENOUS  THROMBOSIS 

Case  XIX. — Gatay  (1895).  Woman,  aged  twenty-eight  years.  Ten 
years  ago  acute  rheumatism  and  endocarditis,  followed  by  palpitation  and 
articular  pains.  A  few  days  before  admission  patient  was  seized  with  chills, 
followed  by  dyspnoea.  On  admission,  cyanosis,  oedema  of  lower  extremities, 
areas  of  pulmonary  consolidation,  disorderly  action  of  heart;  pulse  small 
and  intermittent;  albuminuria;  temperature  39.8°  C.  Four  days  later  hard 
oedema  of  left  arm,  most  marked  in  lower  part,  appeared.  Fluid  in  wrist- 
joint.    Hard  venous  cord  on  inner  side  of  left  upper  arm  was  felt. 

Autopsy. — Much  hypertrophy  and  dilatation  of  heart;  tbe  right  ventricle 
markedly  dilated  and  tricuspid  valve  relatively  insufficient;  mitral  valve 
tbickened,  retracted,  and  incompetent;  old  fibrous  plaques  on  endocardium; 
no  fresh  endocarditis;  pulmonary  infarcts.  Left  brachial  vein  swollen  and 
filled  with  a  red,  adherent,  centrally  softened  thrombus,  10  cm.  long;  venous 
wall  above  and  below  thrombus  red  and  thickened. 

Case  XX. — Kahn  (from  Hanot's  clinic)  (1896).  Woman,  aged  fifty-two 
years.  Seven  years  ago,  influenza,  followed  by  some  oedema  of  legs,  which 
soon  disappeared.  For  four  months  before  admission,  cough,  weakness, 
oedema  of  legs,  loss  of  flesh.  On  admission,  cardiac  hypertrophy,  systolic 
murmur  at  apex  transmitted  into  axilla;  no  murmur  at  base;  pulse  100, 
small,  soft;  radials  sclerotic;  external  jugular  turgid,  but  without  pulsation; 
respirations  rapid  and  labored ;  oedema  of  lower  extremities,  emaciation. 
Ten  days  after  admission  painless  oedema  of  right  hand  and  forearm  ap- 
peared. Temperature,  38.3°  C.  Subcrepitant  rales  at  base  of  lungs.  The 
oedema  rapidly  spread,  so  as  to  involve  the  whole  of  right  arm  and  corres- 
ponding mammary^  region.  There  was  no  pain.  The  skin  was  colder  than 
on  the  left  side  and  somewhat  mottled  with  violet  patches.  Dyspnoea  in- 
tense, respiration  42,  urine  albuminous,  sputum  bloody,  temperature  39°  C. ; 
delirium  and  death  in  coma  about  three  weeks  after  onset  of  thrombosis. 

Autnpi^y. — -Hypertrophy  of  the  whole  heart,  right  cavities  much  dilated, 
mitral  valve  indurated,  thickened,  retracted,  insufficient  without  stenosis; 
other  valves  normal,  fibrous  myocarditis.  Fluid  in  left  pleura,  pulmonary 
infarcts,  chronic  passive  congestion  of  liver  and  kidneys,  spleen  swollen  and 
soft.  Tbere  are  five  or  six  enlarged  glands  near  the  riglit  subclavian  vein, 
which  is  completely  filled  with  a  reddish,  fibrinous,  firm,  non-adherent 
thrombus  4  cm.  long,  extending  to  the  origin  of  the  axillary  vein.  No 
thrombi  in  collateral  veins.  On  microscopical  examination,  coats  of  throm- 
bosed vein  appear  tiiickened,  and  capillaries  in  outer  wall  dilated. 

Case  XXI. — Mader  (1897).  Woman,  aged  forty-five  years.  Repeated 
attacks  of  articular  rheumatism,  followed  by  palpitation,  dyspnoea,  and 
(pdoma  of  lower  extremities.  On  admission  evidences  of  stenosis  and  in- 
sufficiency of  the  mitral  and  tricuspid  valves.  Marked  ascites.  Three  weeks 
later  patient  com])hune(l  of  great  tension  in  veins  of  arms  and,  in  fact,  these 
iKX-ame  enonnously  distended,  a.s  did  also  the  cervical  and  upper  thoracic 
veins.  Collateral  veins  could  be  traced  to  the  epigastric  veins.  There  was 
vertigo,  and  tbe  lips  became  cyanosed.  With  the  establishment  of  a  collateral 
circulation  there  was  gradual  improvement  in  the  symptoms.  The  diagnosis 
was  thrombosis  of  both  innominate  veins,  possibly  also  of  superior  vena  cava, 
complicating  tbe  valvular  affections  mentioned. 


IN  CAEDIAC  DISEASE  273 

Case  XXII. — Helen  Baldwin  (1897).  Girl,  aged  nineteen  years.  Three 
attacks  of  rheumatic  fever,  the  last  seven  years  ago.  Five  weeks  ago  oedema 
of  the  feet.  A  few  days  before  admission,  began  to  suffer  from  pain  in  left 
axilla  and  left  side  of  neck,  also  from  swelling  of  the  left  side  ot  neck.  The 
latter  at  first  would  disappear  in  the  erect  posture.  Amenorrhoea.  On  ad- 
mission, great  weakness,  oedema  of  both  legs,  cyanosis,  dyspnoea,  respirations 
40,  pupils  dilated;  pulse  108,  small,  rapid,  and  compressible;  marked  en- 
largement of  heart,  double  aortic  and  mitral  murmurs,  ascites,  enlargement 
of  liver,  albuminuria,  granular  and  hyaline  casts,  quantity  of  urine  dimin- 
ished, sp.  gr.,  1033.  On  left  side  of  neck  is  a  hard,  tender  swelling  of  lower 
part  of  external  jugular  vein,  which  is  tortuous.  There  is  a  hard  cord  in 
left  axilla,  extending  for  about  five  inches  down  the  arm.  Left  arm  oedema- 
tous  and  pale.  The  next  day  external  jugular  vein  was  felt  as  a  cord  up  to 
one-half  inch  of  lobule  of  ear.  OEdema  of  whole  left  side  of  neck.  Signs 
of  beginning  double  pneumonia.  For  five  days  there  was  noted  a  persistently 
low  temperature  when  measured  by  tliermometer  in  mouth,  whereas  that  by 
the  rectum  was  6  to  7.8  degrees  higher.  Bloody  expectoration  on  the  fifth 
day.    Death  six  days  after  admission. 

Autopsy. — General  oedema,  ascites,  double  hydrothorax,  marked  hyper- 
trophy of  heart,  the  auricles  extremely  dilated,  chronic  changes  in  all  of  the 
valves,  the  most  marked  being  stenosis  and  insufficiency,  of  the  mitral  valve, 
the  edges  of  tricuspid  valve  thickened  and  curled.  Pulmonary  congestion 
and  infarcts  and  early  stage  of  double  lobar  pneumonia.  Chronic  passive 
congestion  of  abdominal  viscera.  Firm  thrombi  fill  the  left  innominate, 
subclavian,  external  and  internal  jugular  veins,  extending  nearly  to  lobe  of 
ear.  TfCins  of  extremities  could  not  be  further  examined.  Enlarged  lymph 
nodes  along  trachea,  not  pressing  on  veins.  Small  extravasation  of  blood 
along  left  side  of  trachea  and  behind  the  left  auricle.  On  microscopical 
examination  the  thrombi  were  found  to  be  partly  organized.  There  was 
marked  chronic  thickening  of  the  intima  of  the  subclavian  vein,  which  was 
believed  to  be  the  starting-point  of  the  thrombus. 

Case  XXIII. — Huchard  (1897).  ^Yoman,  aged  twenty-four  years.  Seven 
years  ago  had  articular  rheumatism  with  cardiac  complication,  followed  by 
mitral  stenosis.  Painful  swelling  of  left  arm  appeared  during  convalescence 
from  an  undetermined  febrile  disease.  On  admission  severe  dyspnoea ;  pulse 
rapid,  small,  irregular;  expectoration  bloody,  urine  slightly  albuminous,  no 
cedema  of  lower  extremities.  Painful,  hard  oedema  of  entire  left  arm,  wath 
prominence  of  superficial  veins,  and  hard,  sensitive,  voluminous,  venous 
cords.    Death  in  coma  nine  days  after  admission. 

Autopsy. — Double  hydrothorax,  pulmonary  infarcts,  slight  ascites,  nut- 
meg liver.  Heart  weiglied  450  grms. ;  buttonhole  mitral  orifice  causing  ex- 
treme stenosis,  slight  narrowing  of  tricuspid  orifice,  and  marked  dilatation 
of  right  auricle.  Large  stratified  thrombus  in  left  auricle.  A  few  pericardial 
adhesions.  Left  brachial  vein  markedly  dilated,  and  filled  in  upper  part 
with  an  adherent  thrombus  3  cm.  long,  starting  from  a  valvular  pocket. 

Case  XXIV. — Huchard  (1897).  Male  'W'ith  mitral  stenosis  and  throm- 
bosis of  veins  of  left  lower  extremity.    No  other  details. 


274  VENOUS  THROMBOSIS' 

Case  XXV. — Nicolle  and  Robineau  (1897).  Girl,  aged  sixteen  and  a  half 
years.  Repeated  attacks  of  rheumatism  during  last  four  years.  Chief  symp- 
tom on  admission,  respiratory  distress;  no  oedema.  Four  months  after 
admission  patient  felt  pain  in  the  left  side  of  neck  and  head,  and  a  hard, 
painful  cord,  5  to  10  cm.  long,  was  detected  in  the  course  of  the  left  external 
jugular  vein.  Three  days  later  the  thrombus  had  extended  and  painful 
oedema  of  left  side  of  neck  and  face  appeared.  Superficial  veins  dilated; 
urine  slightly  albuminous.  'J' en  days  after  first  symptoms  of  thrombosis 
entire  left  upper  extremity  l>ecame  cedematous.  Expectoration  bloody, 
ffidema  increased,  and  appeared  also  in  lower  extremities.  Death  occurred 
a  little  less  than  a  month  after  the  beginning  of  the  thrombosis. 

Autopsy. — Mitral  orifice  narrowed,  numerous  hard,  papillary  vegetations 
on  borders  and  surface  of  mitral  segments,  also  on  the  aortic  valves  and  the 
free  borders  of  the  tricuspid.  Chordae  tendinea3  of  mitral  valve  shortened. 
Hydrothorax,  many  pulmonary  infarcts,  pneumonia  of  left  lower  lobe. 
Thrombosis  of  left  external  jugular  vein  and  branches  and  of  subclavian  vein. 
Thrombus  black,  rather  soft,  slightly  adherent,  unorganized.  Venous  walls, 
especially  inner  coat,  thickened.  Swollen,  hemorrhagic  lymph  glands  sur- 
round the  thrombosed  veins.    Tissues  of  neck  very  o^dematous. 

Case  XXVI. — Poynton  (from  service  of  Dr.  Lees),  (1898).  Girl,  aged 
nineteen  years.  Very  severe  attack  of  rheumatic  fever,  lasting  thirteen 
weeks,  nine  months  before  admission.  Swelling  of  legs  and  abdomen  noticed 
two  months  before  admission,  and  a  few  days  before  admission  left  arm  sud- 
denly began  to  swell.  On  admission  great  pallor  and  distress,  evidences  of 
advanced  organic  disease  of  heart,  systolic  apical  murmur,  accentuated  sec- 
ond pulmonic  sound;  pulse  90,  irregular  in  force  and  rhythm;  oedema  of 
legs  and  thighs,  of  upper  extremities  and  upper  part  of  chest,  the  left  arm 
and  hand  being  very  much  swollen;  impairment  of  resonance  and  respira- 
tory sounds  over  bases  of  limgs,  liver  large  and  tender,  conjunctivae  icteric, 
urine  somewhat  albuminous,  temperature  subnormal  and  continuing  so 
througliout  ilhiess.  Death,  preceded  by  cerebral  symptoms  and  coma,  about 
two  weeks  after  admission, 

Aiifopsy. — Totally  adherent  pericardium,  evidences  of  old  rheumatic  endo- 
carditis; aortic,  mitral,  and  tricuspid  valves  incompetent,  and  mitral  orifice 
slightly  narrowed;  cavities  dilated,  especially  right  ventricle;  weight  of 
heart,  sixteen  ounces.  Pleura^  adherent.  Chronic  passive  congestion  of  vis- 
cera. Adherent  firm  thrombi  filled  both  innominato  and  both  internal  jugu- 
lar veins,  the  lower  end  of  left  internal  jugular  being  white,  narrowed,  and 
very  firm.  Adherent  mural  thrombosis  in  up})er  part  of  superior  vena 
cava.    ^Mediastinal  tissues  a}dematous.    Brain  generally  soft  and  cedematous. 

Case  XXVII. — Po}iiton  (from  service  of  Dr.  Cheadle),  (1898).  Woman, 
aged  twenty-one  years.  In  childhood  scarlet  fever,  followed  by  rheumatic 
fever.  Two  years  ago  second  attack  of  rheumatism.  Present  illness  begaii 
gradually  with  weakness,  dys[)na^a,  and  n^lema  of  legs  and  face.  On  admis- 
sion anaemia,  (inlema  of  legs,  face  puffy,  bronchitic  sounds,  harassing  cough, 
systolic  thrill,  loud  systolic  munnur  over  front  and  back,  dilatation  of  heart. 
Temperature  101°  F. ;  respirations  28;  pulse  128,  of  low  tension.  Urine 
albuminous,  sp.  gr.,  1020,  contained  blood  and  casts.  Liver  and  spleen 
enlarged.     Irregular  pyrexia  and  sweating  continued  throughout  illness  in 


m  CARDIAC  DISEASE  275 

hospital.  Twelve  days  after  admission  pain  in  wrists  and  along  inside  of 
left  forearm.  CEdema  of  face,  which  had  almost  disappeared,  returned, 
especially  on  left  side.  Irreioilarity  of  pulse,  orthopnoca,  symptoms  of  renal 
infarction  and  pneumonia  appeared,  and  death  occurred  five  and  a  half  weeks 
after  admission. 

Autopsy. — Heart  weighed  14  ounces,  all  its  cavities  much  dilated;  hoth 
ventricles  and  left  auricle  hypertrophied ;  muscle  pale;  mitral  orifice 
widened;  numerous  exul)erant  vegetations  of  mitral  segments,  also  on  endo- 
cardium of  left  auricle  and  left  ventricle ;  chordae  tendineffi  ulcerated  through  ; 
other  valves  normal,  except  slight  widening  of  tricuspid  orifice.  Pulmonary 
congestion;  pneumonia  of  left  lower  lobe;  chronic  passive  congestion  of 
abdominal  viscera,  with  infarcts  in  spleen  "and  kidneys  (microscopically  no 
evidence  of  interstitial  inflammation  or  chronic  nephritis).  Left  internal 
jugular,  from  junction  ^vith  subclaWan  vein  to  angle  of  jaw,  occluded  by  a 
thrombus,  which  was  pale  and  adherent  to  wall,  especially  in  lower  part, 
where  vein  was  cord-like.  Innominate  vein  and  right  jugular  not  thrombosed. 
Brain  normal.  On  microscopical  examination  no  micro-organisms  found  in 
cardiac  vegetations  or  in  thrombus.  Diplococci,  staining  by  Gram,  in  pneu- 
monic area.  Sections  of  left  internal  jugular  showed  organizing  thrombus, 
without  distinct  thickening  of  venous  wall.  Walls  of  right  jugular  normal. 
(No  mention  of  cultures.) 

Case  XXYIII. — Poynton  (from  service  of  Dr.  Cheadle),  (1898).  Girl, 
asred  nine  years.  Two  years  ago  scarlet  fever,  since  which  heart  was  affected. 
For  three  weeks  before  admission,  thoracic  pain  and  cough,  and  for  one  week 
dropsy.  On  admission,  February  19th,  pallor,  with  some  cyanosis ;  orthop- 
noea ;  fingers  clubbed ;  cedema  of  lower  extremities,  anterior  chest  wall  and 
face;  some  ascites;  marked  increase  of  cardiac  dulness  to  right  and  left: 
precordial  bulging;  epigastric  pulsation  ;  systolic  and  diastolic  thrill ;  double 
mitral  and  aortic  murmurs ;  doul)tful  pericardial  friction  rub ;  impaired 
resonance  and  respiratory  sounds  over  bases  of  lungs ;  scattered  bronchitic 
rales ;  liver  enlarged  and  |)ulsating.  Temperature  9T.4°  F. ;  respirations  30 ; 
pulse  100,  irregular,  weak  and  small;  urine,  1025,  contained  albumin  and 
blood,  without  casts.  Improvement  until  March  10th,  wlien  pleural  friction 
was  heard  in  left  axilla  and  dulness  at  left  base,  without  rise  of  temperature. 
Again  improvement  until  April  lOtli,  wlicn  pulmonary  symptoms  reappeared 
and  swelling  of  axillary  glands  was  noticed.  Heart  more  dilated,  pulse 
feebler.  13th :  left  side  of  face  swollen.  16th :  marked  (vdema  of  right  side 
of  neck,  eyelids,  and  lips:  face  purple:  both  sides  of  neck  tense,  painful  to 
touch  and  on  movement :  temperature  subnormal.  17th  :  right  arm  began  to 
swell,  shortly  afterward  oedema  of  left  arm  and  chest;  patient  apatlietie. 
18th:  drowsiness,  cyanosis,  sudden  dyspnoea,  with  symptoms  of  collapse. 
19th:  tender  oedema  of  right  arm  extreme.  2nt.h :  two  firm  cords  felt  in 
lower  part  of  neck ;  legs  and  fi'et  a  little  swollen ;  area  of  cardiac  dulness 
enormous:  loud  pericardial  friction,  crepitation  over  both  lungs:  urine 
scanty,  slightly  albuminous,  no  blood.    Death  April  21st. 

Autopsy. — Acute  sero-fibrinous  pericarditis:  all  cardiac  cavities  dilated 
and  hypertrophied,  the  right  relatively  more  than  the  left.  IMitral  and  tri- 
cuspid valves  incompetent:  fresh  vegetations  on  aortic,  mitral,  and  tricuspid 
valves.    Usual  visceral  changes  secondarv  to  advanced  cardiac  disease.    Ob- 


276  VENOUS  THKOMBOSIS 

literati ve  thrombosis  of  superior  vena  cava  in  its  upper  two-thirds,  both 
innominate,  subclavian,  internal  and  external  jugular,  and  axillary  veins, 
and  the  left  inferior  thyroid  vein.  Small  adherent  mural  thrombus  in  left 
branchial  vein.  The  oldest  parts  of  the  thrombus  were  in  the  lowest  portions 
of  the  internal  jugular  veins  and  the  left  innominate,  which  were  white, 
small,  and  firm,  and  adherent  to  surrounding  tissues.  Beyond  these  older 
thrombi  the  vessels  were  bulged  with  soft  clot.  The  thrombus  in  the  superior 
cava  was  soft,  pale,  non-adherent,  except  in  its  upper  part. 

Cultures  and  films  from  pericardial  exudate  and  blood-clot  negative;  sec- 
tions of  soft  clot  in  superior  cava  and  of  thrombus  in  right  axillary  showed 
no  micro-organisms.  Thrombi  were  undergoing  organization  in  older  parts. 
Early  phlebo-sclerosis,  apparently  secondary  to  thrombus,  in  older  throm- 
bosed vessels.  Venous  wall  not  tliickened  where  thrombus  was  fresh  and  not 
adherent.  Interstitial  myocarditis  in  subpericardial  layers  and  beneath  in- 
flamed endocardium. 

The  most  remarkable  feature  of  the  foregoing  twenty-eight  cases  of  venous 
thrombosis  in  heart  disease  is  the  location  of  the  thrombi:  twenty-four 
were  thromboses  of  veins  conveying  blood  from  the  upper  extremities  or 
the  neck,  or  both,  mostly  of  the  left  side,  and  only  four  were  thromboses 
of  the  veins  supplying  the  lower  extremities.  I  do  not  suppose  that  these 
numbers  represent  the  correct  ratio  between  upper  and  lower  venous  throm- 
bosis in  heart  disease,  for  thrombosis  of  veins  of  the  lower  extremities  in 
tliis  condition  is  much  more  likely  to  be  overlooked  in  consequence  of  the 
more  common  and  greater  cedema  of  the  lower  limbs,  and  is  also  much 
less  likely  to  be  reported.  How  often  it  is  overlooked  can  be  at  present 
only  a  matter  of  conjecture,  but  it  is  not  probable  that  such  thrombosis  is 
at  all  frequent.  In  fact,  the  comparative  infrequency  of  peripheral  venous 
thrombosis  in  cardiac  disease  is  in  itself  a  matter  of  interest,  in  view  of 
the  slow,  feeble  and  irregular  venous  circulation,  and  of  the  frequency  of 
so-called  marantic  thrombi  in  the  heart  itself  during  the  failure  of  com- 
pensation. The  relatively  small  liability  to  venous  thrombosis  under  such 
conditions  of  the  circulation  is  one  of  many  evidences  that  mere  slowing 
of  the  blood  current  is  not  an  efficient  cause  of  thrombosis. 

Even  allowing  for  a  considerable  increase  in  the  number  of  instances 
of  thrombisis  of  the  veins  of  the  lower  extremities  as  the  result  of  more 
thorough  search  in  cases  of  heart  disea.^e,  the  relatively  large  numl)er  of 
obtervations  of  thrombosis  of  the  upper  veins  revealed  in  my  collection  of 
ca-ces  still  remains  most  remarkable.  Bouchut  places  the  ratio  of  venous 
thromboses  of  the  upper  extremity  to  those  of  the  lower  at  one  to  fifty. 
Of  sixty-seven  cases  of  peripheral  venous  thrombosis  in  our  autopsy  records 
at  the  Johns  Hopkins  Hospital,  only  one  was  of  the  upper  extremities, 
although  several  instances  of  the  latter  have  been  observed  clinically  in 
the  hospital.    Moreover,  the  four  instances  above  recorded  of  venous  throm- 


IN  CARDIAC  DISEASE  277 

bosis  of  the  lower  extremities  in  heart  disease  had  little  in  common  with 
the  remaining  cases.  Two  were  in  old  persons,  with  some  arterial  atheroma, 
and  of  two  no  satisfactory  history  is  given.  The  thrombosis  was  on  the 
left  side  in  three  and  bilateral  in  one,  thus  conforming  to  the  rule.  As 
will  appear  from  an  analysis  of  the  remaining  twenty-four  cases,  the  venous 
thromboses  of  the  neck  and  arms  in  cardiac  disease  constitute  a  separate 
and  distinct  group,  characterized  by  special  features  of  unusual  interest. 

Analysis  of  Twenty-four  Cases   of  ,  Thrombosis   of  Veins  of 
Neck,  Arm  and  Chest  in  Heart  Disease 

Sex. — Seventeen  cases  were  females,  five  of  males,  and  of  two  the  sex 
is  not  stated.  While  the  total  number  of  cases  is  too  small  to  warrant  per- 
centage estimates,  there  can  be  no  doubt  that  females  are  much  more  dis- 
posed to  this  form  of  thrombosis  than  males.  Whether  this  disposition  is 
more  than  an  expression  of  the  greater  liability  of  females  to  the  mitral 
lesions  present  at  the  ages  in  the  cases  observed,  I  must  leave  an  open  ques- 
tion.   The  figures  seem  somewhat  out  of  proportion  to  this  great  tendency. 

Age. — One  patient  was  nine  years  old,  6  were  between  ten  and  twenty, 
3  between  twenty  and  thirty,  3  between  thirty  and  forty,  2  between  forty  and 
fifty,  3  between  fifty  and  sixty,  and  of  6  the  age  is  not  stated.  Of  the  18 
patients  with  thrombosis  of  the  neck  and  arms  whose  ages  are  stated,  nearly 
one-half  (8)  were  between  fifteen  and  thirty  years  of  age.  The  youngest 
was  nine  and  the  oldest  fifty-three. 

Valvular  Lesion. — In  two  cases  the  exact  nature  of  the  valvular  lesion  is 
not  stated.  Of  the  remaining  22  cases,  there  was  organic  disease  of  the 
mitral  valve  in  21 ;  in  the  exceptional  case  there  was  aortic  insufficiency 
with  relative  mitral  incompetence. 

The  mitral  lesion  is  described  as  insufficiency  in  9  cases,  as  stenosis  in 
6,  and  as  stenosis  and  insufficiency  in  6.  In  the  last  group  there  were  at 
least  three  instances  of  extreme  stenosis.  The  aortic  valves  were  affected  in 
10  cases,  in  all  of  these  there  being  incompetence,  sometimes  also  with 
obstruction. 

The  organic  valvular  lesion  was  limited  to  the  mitral  valve  in  12  cases, 
to  the  aortic  valve  in  one,  to  the  mitral  and  aortic  valves  in  6,  to  the  mitral, 
aortic  and  tricuspid  valves  in  two,  and  in  one  case  all  of  the  valves  were 
organically  diseased. 

In  all  of  these  cases  there  was  chronic  disease  of  the  valves.  In  five 
cases  there  appears  to  have  Ix^en  a  fresh  endocarditis  engrafted  upon  the 
chronic  affection,  and  it  is  possible  that  in  some  other  cases  this  was  present, 
but  in  the  majority  of  tlie  observations  there  was  not  acute  endocarditis. 

Adherent  pericardium  was  noted  in  four  cases,  acute  pericarditis  in  one. 


278  VEXOUS  THROMBOSIS 

It  is  evident  tliat  the  association  of  thrombosis  of  the  upper  veins  with 
valvular  disease  of  the  heart  is  almost,  although  not  wholly,  limited  to 
cases  of  mitral  disease,  those  of  mitral  stenosis,  with  or  without  insufficiency, 
taking  the  lead.  The  preponderance  of  females  and  of  patients  under  mid- 
dle age  is  thus,  at  least  in  great  part,  explained.  That  the  complication 
may  occur  in  men  in  advanced  life  with  general  arterio-sclerosis  and  chronic 
B right's  disease  associated  with  cardiac  disease  is  shown  by  Case  V. 

Relation  to  Rheumatism. — As  is  to  be  expected  from  its  nature,  the  val- 
vular lesion  was  most  frequently  caused  by  acute  articular  rheumatism,  of 
which  there  was  a  distinct  history  in  a  little  over  half  the  eases,  but  other 
infectious  diseases  (scarlet  fever,  pneumonia,  influenza,  puerperal  infection, 
diphtlieria,  sy]>liilis,  and  chorea)  also  had  a  share  in  the  causation.  In  a 
number  of  instances  the  valvular  trouble  seems  to  have  developed  insidi- 
ously.    There  is,  tlierefore,  nothing  peculiar  in  the  antecedent  histories. 

Although  several  observers  regarded  the  occurrence  of  the  thrombosis  as 
a  direct  manifestation  of  rheumatism,  only  in  three  cases  was  there  any 
painful  swelling  of  a  joint  present  shortly  before  or  during  the  attack  of 
thrombosis. 

Relation  to  Cardiac  Insufficiency. — In  the  great  majority  of  cases  the 
thrombosis  appeared  during  a  condition  of  failure,  generally  extreme  failure, 
of  compensation  of  advanced  mitral  disease.  The  frequency  with  which  pul- 
monary infarction  was  observed  at  autopsy  is  one  of  the  many  evidences  of 
this.  Eelative  insufficiency  of  the  tricuspid  valve  and  pulsation  of  the 
cervical  veins  were  noted  in  many  of  the  cases,  and  very  likely  were  present 
in  some  of  those  in  whose  histories  they  are  not  noted,  but  it  does  not 
appear  that  these  conditions,  although  contributory,  are  necessary  factors 
in  the  causation  of  the  thrombosis. 

Location  of  the  Thrombi. — A  fact  which  at  once  arrests  attention  is  that 
the  thrombosis  affected  veins  of  the  left  side  in  22  out  of  the  24  cases,  of 
which  15  were  unilateral  and  7  bilateral.  In  only  two  cases  were  veins  of  the 
right  side  alone  affected.  Bilateral  thrombosis  is,  therefore,  more  common 
than  unilateral  right-sided  thrombosis,  and  unilateral  left-sided  throm- 
bosis is  by  far  the  most  common  form  of  the  disease.  The  hypotheses  in 
explanation  of  this  distribution  will  be  considered  later. 

In  7  cases  the  throml)osis  was  apparently  limited  to  the  arm  veins,  in 
one  to  veins  of  the  neck,  and  in  16  cases  veins  both  of  the  neck  and  arms  were 
thrombosed.  In  one  case  the  thrombus  was  confined  to  the  left  subclavian 
vein,  in  one  to  the  left  internal  jugular,  and  in  two  to  tlie  left  l)rachial.  In 
all  the  other  cases  more  than  one  vein  was  thrombosed,  the  combination 
varying  in  different  cases,  the  most  common  being  continuous  thrombosis  of 
tlie  left  innominate,  iiitrrnal  iiiid  external  juguliir.  sulx-lavian,  and  iLxillary 


IN  CAEDIAC  DISEASE  279 

veins.  The  superior  vena  cava  was  partly  or  wholly  thrombosed  in  6  cases 
(confirmed  by  autopsy  in  four),  fhe  innominate  in  11  (confirmed  by  autopsy 
in  8),  the  internal  jugular  in  14  (autopsy  in  11),  the  external  jugular  in 
12  (autopsy  in  8),  the  subclavian  in  16  (autopsy  in  13),  the  axillary  in 
11,  the  brachial  in  6,  the  inferior  thyroid  in  1,  and  the  left  lateral  sinus 
of  the  brain  in  1. 

The  commonest  starting-point  for  the  thrombus  was  the  lowest  part  of 
the  left  internal  jugular  (bulb),  or  of  the  left  external  jugular  vein  and  the 
left  innominate  or  subclavian  vein  near  the  entrance  of  the  jugulars.  In 
many  cases  this  was  clearly  demonstrated  by  the  appearances  of  the  throm- 
bus and  the  venous  wall  in  these  situations.  The  thrombus  may,  however, 
originate  in  otlier  veins,  especially  in  valvular  pockets  of  the  veins  in  the 
left  arm. 

The  most  extensive  thrombosis  was  that  recorded  by  Popiton  (Case 
XXVIII),  in  wliicli  there  was  occlusion  of  the  superior  vena  cava  in  its 
upper  two-thirds,  of  both  innominate,  internal  and  external  jugular,  sub- 
clavian, and  axillary  veins,  and  the  left  inferior  thyroid  vein. 

Tlie  thrombus  was  generally  a  continuous  one,  apparently  originating 
in  one  vein,  whence  it  was  propagated  into  peripheral  veins  and  also  cen- 
trally, even  into  the  superior  vena  cava. 

Characters  of  the  Thrombi  and  Venous  Walls. — The  thrombi  were  mixed, 
the  prevailing  color  being  dark  red.  The  older  parts  were  gray  or  reddish- 
gray  and  adherent.  The  fullest  description  of  the  microscopical  characters 
is  that  which  I  have  recorded  under  Case  I.  In  a  few  instances  the  throm- 
bus was  centrally  softened,  but  in  most  it  was  solid  and  completely  occlud- 
ing except  at  the  ends  and  except  in  the  mural  thrombus  mentioned  in 
Case  XXVIII.  The  older  thrombi  were  usually  more  or  less  advanced  in 
organization.  Bacteria  were  searched  for  in  apparently  only  tliree  cases,  and 
were  found  only  in  my  Case  I,  tbe  organism  here  being  Streptococcus 
pyogenes. 

In  7  cases  it  was  noted  that  the  wall  of  the  thrombosed  vein  was  thickened, 
but  this  thickening  was  generally  regarded  as  secondary  to  the  forma- 
tion of  the  thrombus,  which  was  two  or  more  weeks  old.  Only  in  Helen 
Baldwin's  case  and  in  Case  V  is  it  distinctly  stated  that  the  appearances 
indicated  phlebo-sclerosis  (subclavian  vein)  antedating  the  thrombus.  In 
two  of  Poynton's  cases  the  jugular  and  innominate  veins,  where  the  oldest 
part  of  the  thrombus  was  situated,  were  narrowed,  white,  and  firm,  aaid  a 
similar  condition  was  noted  by  Eobcrt.  Chronic  disease  of  the  veins  evi- 
dently plays  only  a  minor  part  in  the  causation  of  thrombosis  in  these 
cases. 


280  VENOUS  THROMBOSIS' 

Effect  and  Symptoms. — The  anatomical  lesions  outside  of  the  vessels 
directly  referable  to  the  thrombosis  were  oedema  of  the  tissues  and  swelling 
of  the  lymphatic  glands.  The  oedema  cannot  always  be  explained  entirely  as 
the  result  of  venous  congestion,  but  is  in  part  inflammator}',  as  is  true  in 
general  of  the  oedema  in  phlegmasia.  Swollen  lymphatic  glands,  which  were 
sometimes  hemorrhagic  or  pigmented,  were  often  observed  in  the  neighbor- 
hood of  the  thrombosed  veins.  This  swelling  was  generally  acute  and  evi- 
dently secondar}'  to  the  thrombosis,  but  Kahn  attributed  the  exceptional 
localization  of  the  thrombus  in  the  right  subclavian  vein  in  his  case  (XX) 
to  the  pressure  of  previously  enlarged  glands.  Poynton  noticed  cerebral 
oedema  in  one  of  his  cases  which  had  manifested  brain  symptoms. 

The  local  symptoms  are  the  usual  ones  of  venous  thrombosis:  pain, 
tenderness,  oodema,  the  presence  of  hard,  sensitive  venous  cords,  and  dis- 
tention of  superficial  veins.  Often  the  pain,  sometimes  the  oedema,  was 
the  first  s}'mptom.  The  cedematous  swelling  may  be  hard  and  brawny, 
or  softer,  as  in  dropsy.  In  some  cases  the  pain  and  cedematous  swelling 
were  first  manifest  in  the  neck,  in  others  in  the  arm.  Extension  of  the 
oedema  to  the  front  and  side  of  the  upper  part  of  the  thorax  was  repeatedly 
noted.  Occasionally  the  side  of  the  face  corresponding  to  the  thrombosis 
was  cedematous.  The  extent  and  distribution  of  the  oedema,  while  depen- 
dent in  the  first  instance  upon  the  extent  and  location  of  the  thrombosis, 
were  influenced,  as  is  usual  in  venous  thrombosis,  by  other  factors,  so  that 
they  varied  much  in  cases  with  the  same  distribution  of  the  thrombi. 

Constitutional  symptoms  of  the  thrombosis,  if  present,  could  not  readily 
be  separated  from  those  of  associated  conditions.  The  marked  difference 
between  the  buccal  and  rectal  temperatures  observed  in  Helen  Baldwin's 
case  (XXII)  is  interesting.  Cerebral  symptoms,  attributed  by  Poynton 
to  cerebral  oedema,  were  observed  in  a  few  cases. 

As  is  illustrated  by  Case  V,  the  only  symptom  of  the  thrombosis  may 
be  oedema,  usually  of  the  left  arm,  the  patient  suffering  little  or  no  incon- 
venience from  the  swelling,  and  the  affection  being  recognized  sometimes 
almost  accidentally. 

Ilanot,  in  1874,  called  attention  in  a  short  note  to  the  more  rapid  onset 
and  the  longer  persistence  of  oedema  of  the  left  arm,  as  compared  with 
the  right,  in  cardiac  affections,  and  he  explained  this  peculiarity  by  the 
greater  length  and  obliquity  of  the  left  innominate  vein.  It  would  appear, 
therefore,  that  oedema  limited  to  or  in  excess  in  the  left  arm  in  heart 
disease  should  not  be  rogard(>d  as  positive  evidence  of  thrombosis  of  veins 
conveying  blood  from  this  extremity.  While  this  is  doubtless  true,  it  is 
desirable,  in  view  of  the  cases  reported  in  this  paper,  to  search  carefully 
in  these  instances  for  other  evidences  of  thrombosis. 


IN  CARDIAC  DISEASE  281 

Prognosis. — Of  the  twenty-four  cases,  twenty  ended  fatally  and  four 
(Case  II,  VII,  XIII,  and  XXI)  recovered.  The  gravity  of  the  prognosis 
doubtless  mainly  results  from  the  circumstance  that  the  occurrence  of  the 
thrombosis  is  in  itself  an  index  of  extreme  failure  of  compensation  of  the 
valvular  lesion,  being  sometimes  scarcely  more  than  a  terminal  event.  We 
know  that  occlusion  of  the  superior  vena  cava  and  its  large  tributaries,  due 
to  other  causes,  may  be  completely  compensated  by  the  development  of  a 
collateral  circulation,  and  there  are  instances  of  this  even  in  the  present 
group  of  cases  (VII  and  XXI),  so  that  it  is  less  the  venous  occlusion  than 
the  condition  of  the  heart  and  the  frequent  presence  of  pneumonia  or 
other  terminal  infections  which  makes  the  issue  so  unfavorable.  In  rare 
instances,  thrombosis  of  the  upper  veins  may  occur  at  a  period  when  the 
compensation  is  not  badly  broken  (Case  II).  Large  pulmonary  embolism 
was  not  observed.  Whether  pulmonary  infarcts,  which  were  frequently 
present,  were  attributable  to  emboli  derived  from  the  venous  thrombi  was 
not  determined.  The  duration  in  the  fatal  cases  of  thrombosis  varied  from 
two  days  to  six  weeks. 

Causation-. — Although  five  of  the  cases  were  reported  as  instances  of 
rheumatic  phlebitis,  it  does  not  seem  to  me  demonstrated  that  even  in  these 
cases  (XII,  XIX,  XXVI,  XXVII,  XXVIII)  this  was  the  correct  explana- 
tion and  it  is  certain  that  the  great  majority  of  cases  cannot  be  explained  in 
this  way.  It  is  true  that  phlebitis,  or  venous  thrombosis,  is  a  genuine,  al- 
though infrequent,  complication  of  acute  rheumatism,  and  there  is  some  evi- 
dence that  it  may  affect  veins  of  the  upper  extremities  somewhat  more  fre- 
quently than  does  thrombosis  due  to  most  other  causes,  but  there  is  no  such 
enormous  preponderance  of  upper  thromboses  as  in  the  class  of  cases  now 
under  consideration.  As  already  mentioned,  the  histories  of  the  cases  do  not 
support  the  view  that  rheumatism  had  more  than  a  minor  share  in  the 
immediate  causation  of  the  thrombosis.  There  is  no  reason,  however,  why 
acute  rheumatism,  like  other  infections,  may  not  directly  participate  in 
the  causation  of  the  venous  thrombosis. 

French  writers  (Peter,  Parmentier,  Kahn,  Huchard)  attribute  the  throm- 
bosis to  cardiac  cachexia  combined  with  circulatory  disturbances.  They  say 
that  this  cardiac  cachexia  (so  designated  by  Andral)  is  something  to  be 
distinguished  from  asystole — that  is,  from  mere  breakage  of  compensation. 
They  bring  this  class  of  thromboses,  therefore,  into  line  with  that  com- 
plicating tuberculosis  and  cancer,  and  explain  the  peculiar  localization  by 
the  particular  disturbances  of  the  circulation  in  cardiac  disease.  The  under- 
lying cause  according  to  this  view,  is  some  alteration  in  the  chemical  composi- 
tion of  the  blood.  It  is  difficult  to  say  how  much  weight  is  to  be  attached  to 
this  explanation.  In  many  cachectic  conditions  there  is  an  increase  in  the 
21 


282  VENOUS  THEOMBOSIS 

blood  platelets,  attributable  probably  to  weakened  resistance  of  the  red  cor- 
puscles, and  some  writers  have  brought  cachectic  thromboses  into  relationship 
with  this  increase.  According  to  van  Emden,  the  number  of  platelets  is 
diminished  in  the  chronic  congestion  of  heart  disease.  I  know  of  no  observa- 
tions concerning  the  number  of  platelets  in  these  cases  of  heart  disease  with 
venous  thrombosis.  I  could  find  nothing  in  the  histories  of  most  of  the  cases 
indicating  any  peculiar  cachexia,  and  I  am  not  inclined  to  regard  this  ex- 
planation of  the  thrombosis  of  heart  disease  as  a  satisfactory-  one. 

The  first  thing  which  needs  explanation  is  the  localization  of  the  throm- 
bosis in  the  veins  receiving  blood  from  the  upper  part  of  the  body,  and 
especially  from  the  left  side.  Hanot  and  Parmentier  explain  the  prefer- 
ence for  the  left  side  by  the  greater  length  and  obliquity  of  the  left  innomi- 
nate vein,  so  that,  like  return  flow  of  blood  from  the  left  leg,  that  from 
the  left  arm  and  left  side  of  the  neck  is  more  difficult  than  from  tlie  right 
side,  this  difficulty  being,  of  course,  most  in  evidence  in  the  venous  conges- 
tion of  uncompensated  cardiac  disease.  Hirschlaff  suggests  that  an  addi- 
tional factor  may  be  the  greater  frequency  of  imperfect  development  and 
of  insufficiency  of  the  valve  near  the  junction  of  the  internal  jugular  and 
subclavian  veins  on  the  left  than  on  the  right  side.  To  these  factors  I 
would  add  pressure,  either  direct  or  indirect,  on  the  left  subclavian  vein 
from  the  dilated  left  auricle  and  dilated  large  pulmonary  vessels.  Popoff 
noted  pressure  from  this  source  on  the  left  subclavian  artery  in  mitral 
stenosis  with  insufficiency  as  a  cause  of  relative  weakness  of  the  left  radial 
pulse  (pulsus  differens).  I  would  refer  to  his  article  for  a  consideration 
of  the  factors  concerned  in  producing  this  pressure.  A  large  accumula- 
tion of  fluid  in  the  left  pleural  cavity,  which  was  noted  in  many  of  the 
cases,  may  also  contribute  to  this  pressure. 

Peter,  in  1873,  was  the  first  to  suggest  that  the  frequency  with  which 
the  thrombus  starts  from  the  lower  ends  of  the  jugulars  is  to  be  explained 
by  the  presence  of  valves  in  this  situation.  I  am  inclined  to  lay  emphasis 
upon  the  readiness  with  which  an  eddying  or  whirling  motion  of  the  blood 
may  be  set  up  in  heart  disease  in  the  lower  ends  of  the  jugulars  and  the 
adjacent  parts  of  the  innominate  and  subclavian  veins.  Von  K^ckling- 
hausen  has  brought  forward  strong  evidence  that  this  whirling  movement 
(Wirl)clbewegung)  of  tlie  blood  is  of  great  importance  in  determining  the 
h)calization  of  thrombi  in  general.  The  valves,  the  bulbous  enlargement 
at  the  lower  end  of  the  internal  jugular,  the  attachment  of  veins  to  fasciae, 
and  the  coming  together  here  at  oblique  and  right  angles  of  currents  of  blood 
with  different  pressures  and  velocities,  seem  well  calculated  to  cause  in  these 
veins  whirling  or  vertical  motion  of  the  blood  current,  especially  in  the 
circulatory   conditions   of  broken  compensation   of  mitral   lesions.     Most 


IN  CAKDIAC  DISEASE  283 

favorable  to  this  peculiar  disturbance  of  the  circulation  would  be  tricuspid 
insufficiency  with  systolic  reflux  of  blood  into  the  veins.  I  would  explain, 
therefore,  the  special  localization  of  the  venous  thrombosis  complicating 
cardiac  disease,  on  the  one  hand  by  the  particular  disturbance  of  the  cir- 
culation, and  on  the  other  by  the  anatomical  disposition  and  structure  of 
the  veins. 

These  factors,  however,  explain  only  why  certain  veins  are  the  seat  of 
election  for  the  thrombi.  The  circulatory  conditions  described  must  often 
exist  within  these  veins  in  uncompensated  cardiac  diseases,  whereas  venous 
thrombosis  is  a  rare  complication  of  heart  disease.  In  the  case  which  first 
directed  my  attention  especially  to  this  subject,  and  which  I  have  here 
reported  as  Case  I,  an  immediately  exciting  cause  for  the  thrombosis  was 
discovered  by  the  demonstration  of  bacteria  in  the  thrombus.  This  is  the 
only  case  in  the  entire  list  in  which  micro-organisms  were  found,  but,  so 
far  as  I  can  gather,  in  only  three  other  cases  were  bacteria  especially  looked 
for,  an<l  it  does  not  appear  that  in  any  of  these  latter  were  cultures  made 
from  the  thrombus.  Such  cultures  are,  of  course,  necessary  in  order  to 
exclude  the  presence  of  bacteria,  and,  indeed,  our  experience  has  been  that 
even  a  negative  result  from  cultures  is  not  absolutely  decisive.  Evidence 
has  accumulated  in  recent  years  in  support  of  the  infectious  origin  of 
many  thrombi.  Dr.  Harris  and  Mr.  Longcope,  who  will  report  their  obser- 
vations later,  have  now  examined  in  my  laboratory  bacteriological ly  forty- 
four  thrombi,  mostly  peripheral  venous  thrombi  of  the  so-called  marantic 
type,  and  in  thirty-four  of  these  have  demonstrated  the  presence  of  bacteria. 
As  has  been  shown  by  Dr.  Flexner  in  my  laboratory,  terminal  infections 
are  not  uncommon  in  heart  disease.  The  histories  and  autopsies  of  many 
of  the  twenty-four  cases  now  under  consideration  revealed  some  infectious 
process,  usually  in  the  lungs,  such  as  bronchitis,  pneumonia,  and  pleurisy. 
While,  therefore,  it  would  be  quite  unwarrantable,  from  existing  evidence, 
to  refer  this  class  of  venous  thromboses  in  cardiac  disease  positively  to 
infection,  this  seems  to  me  at  present  the  most  probable  explanation. 

BIBLIOGRAPHY 

Baldwin,  Helen:    Journ.  Amer.  Med.  Assoc,  August  21,  1897,  p.  371. 

Bouchut:    Gaz.  med.  de  Paris,  1845,  p.  245. 

Cohn:    Klinik  der  embolischen  Gefasskrankheiten,  Berlin,  1860,  p.  118. 

Duguet:    De  I'apoplexie  pulmonaire.    These  de  Concours,  Paris,  1872. 

Gatay:    Contribution  a  I'etude  de  la  phlebite  rhumatismale.     ThSse,  Paris,  1895. 

Hanot:    Comptes  rendus,  Soc.  de  Biologie,  1874,  6  Ser.,  T.  I,  p.  80,  Paris,  1875. 

Hirschlaff:     Betrag   zur   Lehre    und    Casuistik   von   der   Thrombose    der   Vena 

jugularis  interna.,  externa,  und  subclavia.     Inaug.  Diss.,  Berlin,  1893. 
Huchard:    Rev.  gen.  de  clin.  et  de  therap.    (Journ.  de  praticiens),  1897,  p.  787. 


284  YEXOUS  THROMBOSIS  IX  CARDIAC  DISEASE 

Jolly:    De  la  phlegmasia  alba  dolens.    Th6se,  Paris,  1861. 

Kahn  (and  Hanot) :    Arch.  gen.  de  med.,  1896,  II,  p.  469. 

Mader:    Jahrb.  d.  Wiener  K.  K.  Kranken-Anstalten,  IV,  Jahrg.   (1895),  p.   252, 

Wien  u.  Leipzig.,  1897. 
Nicolle  and  Robineau:    La  Normandie  med.,  1897,  XII,  p.  68. 
Ormerod:    Trans.  Path.  Soc,  London,  1889,  XL,  p.  75. 
Parmentier  (and  Hanot):    Arch.  gen.  de  m6d.,  1889,  II,  p.  91. 
Peter:    Legons  de  clinique  medicale,  Paris,  1873,  T.  I,  p.  209. 
Popoff:    Virchow's  Festschrift  (Internat.),  Berlin,  1891,  III,  p.  333. 
Poynton:   Lancet,  1898,  II,  p.  206. 
Ramirez:    Gaz.  med.  de  Paris,  1867,  p.  716. 
Von  Recklinghausen:    Handb.  d.  allgem.  Pathologie,  d.  Kreislaufs  u.  d.  Ernahr- 

ung,  p.  129.     Stuttgart,  1883. 
Robert:    Bull,  de  la  Soc.  Anat.  de  Paris,  4  Ser.,  T.  V,  p.  314.    Paris,  1880. 
Welch:    Allbutt's  System  of  Medicine,  VI,  pp.  198  and  275.    London,  1899. 


MILIARY  ANEURISM  OF  A  BRANCH  OF  THE  GASTRIC  ARTERY ' 

The  patient  was  a  man  about  50  years  of  age,  who  had  not  been  under  the 
observation  of  a  physician  before  tlie  fatal  rupture  of  the  aneurism  occurred. 
His  health  was  not  vigorous,  but  no  definite  clinical  history  of  his  previous 
condition  t  iild  be  obtained.  The  patient  was  seized  during  the  niglit  witii 
profuse  vomiting  of  blood  which  in  a  few  hours  terminated  fatally.  Gastric 
ulcer  was  suspected. 

At  the  post-mortem  examination  the  stomach  was  found  filled  with  dark, 
partly  coagulated  blood.  On  removing  this  a  thick  layer  of  tenacious  bloody 
mucus  coated  the  inner  surface  of  the  stomach.  No  ulceration  of  the 
stomach  could  be  detected.  It  was  only  after  long-continued  search,  which 
was  rendered  unusually  difficult  by  the  adherent  bloody  mucus,  that  a  minute 
loss  of  substance,  not  exceeding  3  or  4  mm.  in  diameter,  was  found  in  the 
mucous  membrane  of  the  posterior  wall  of  the  stomach,  about  midway  between 
lesser  and  greater  curvature  and  pylorus  and  cardia.  In  the  floor  of  this 
perforation  of  the  mucosa  lay  a  small  aneurism  about  the  size  of  a  split  pea. 
Tlie  aneurism  was  of  a  sub-mucous  branch  of  the  coronary  artery  and  it  had 
ruptured  at  the  point  nearest  the  cavity  of  the  stomach  so  that  a  fine  probe 
could  be  passed  through  the  perforation  in  the  mucous  membrane  directly 
into  the  lumen  of  the  artery. 

The  aneurism  was  the  result  of  an  arteritis.  There  existed  a  wide  spread 
endarteritis  obliterans  affecting  the  medium  sized  and  small  arteries  over  a 
large  part  of  the  body,  including  those  of  tlie  stomach,  kidneys,  spleen,  heart 
and  lymphatic  glands.  Although  this  condition  suggested  the  existence  of 
syphilis,  no  further  evidence  of  syphilis  could  be  fomid  at  the  autopsy.  The 
kidneys  were  the  seat  of  advanced  chronic  interstitial  nephritis,  being  small, 
granular  and  with  fibroid  glomeruli.  The  heart  was  hypertrophied  without 
valvular  lesions  and  presented  patches  of  fibroid  induration. 

The  case  is  instructive  on  account  of  the  comparative  infrequency  of 
rupture  of  miliary  aneurism  of  the  stomach  with  fatal  ha^matemesis.  The 
readiness  with  which  such  a  minute  perforation  of  the  gastric  mucous  mem- 
brane might  be  overlooked  at  the  autopsy  is  calculated  to  awaken  scepticism 
regarding  certain  cases  of  fatal  gastrorrhagia  reported  without  demonstrable 
lesion  of  the  stomach  and  therefore  attributed  to  capillary  or  parenchyma- 
tous hemorrhage  in  persons  not  affected  with  cirrhosis  of  the  liver  or  otlier 
conditions  causing  portal  obstruction. 

*  Presentation  of  pathological  specimen  and  report  before  the  Johns  Hopkins 
Hospital  Medical  Society,  October  22,  1S89. 

Johns  Hopkins  Hosp.  Bull.,  Bait.,  1889-90,  I,  12.  285 


DUPLICATURE  OF  ARCH  OF  AORTA  WITH  ANEURISM' 

The  specimen  canie  from  a  negro  43  years  old,  who,  for  six  months  before 
death,  had  suffered  from  paroxysmal  cough,  hoarseness  increasing  to  aphonia, 
dyspnoea  increasing  to  orthopnoea,  pain  in  the  chest  and  loss  of  flesh.  Nine- 
teen years  ago  he  had  acute  articular  rheumatism,  and  some  years  before 
that  pneumonia.  On  admission  he  had  extreme  dyspnaa;  inspiration  was 
short  and  noisy;  expiration  was  much  prolonged  and  rough.  His  pulse  was 
32  and  regular;  respiration,  36 ;  temperature,  97.6°  F.  There  was  moderate 
engorgment  of  the  superficial  veins  of  the  neck.  Sternal  notch  was  oblit- 
erated. Apex  beat  of  the  heart  was  neither  visible  nor  palpable.  There  was 
dulness  at  the  level  of  the  third  rib  and  diminished  resonance  over  the 
sternum  at  this  level.  Heart  sounds  were  normal.  Coarse  and  fine  rales 
were  audible  over  the  posterior  part  of  both  lungs.  Breath  sounds  were 
rough.  The  urine  contained  a  moderate  amount  of  albumen,  with  hyaline 
and  granular  casts.  The  patient  died  suddenly  three  days  after  admission 
to  the  hospital. 

At  the  autopsy  the  lungs  were  found  to  be  moderately  emphysematous  with 
slight  dilatation  of  tlie  bronchi.  There  were  numerous  areas  of  fresh  broncho- 
pneumonia in  the  posterior  lobes  of  both  lungs  and  general  pulmonary 
oedema.  The  kidneys  were  small  and  granular  and  microscopically  showed 
increase  of  connective  tissue,  fibrous  glomeruli  and  atrophied  tubules.  In  the 
cervical  and  portal  lymphatic  glands  were  encapsulated  old  caseous  nodules. 
The  liver,  spleen  and  alimentary  tract  presented  no  noteworthy  lesions. 

The  heart  was  nonnal,  no  changes  being  present  in  the  valves  nor  in  the 
size  of  the  heart  cavities  or  the  thickness  of  their  walls.  On  the  posterior 
wall  of  the  ascending  aorta,  3  cm.  above  the  valves,  is  a  distinct  depression 
5  mm.  in  diameter  and  2  mm.  in  depth,  over  wliich  apparently  normal  intima 
is  continuous.  At  the  point  where  the  innominate  artery  should  be  given 
off  the  aorta  divides  into  two  branches,  a  larger  anterior  and  a  smaller 
posterior  branch  whicli  joins  the  anterior  branch  2  cm.  below  the  origin  of 
the  left  subclavian  artery.  The  posterior  branch  passes  behind  the  trachea, 
between  it  and  the  cosopiiagus,  so  that  the  trachea  passes  through  the  ring 
formed  by  the  two  divisions  of  the  transverse  arch  of  the  aorta.  From  the 
anterior  division  are  given  off  in  their  usual  position  the  left  common  carotid 
and  the  left  subclavian  arteries.    The  beginning  of  the  posterior  trunk  is  the 

'  Presentation  of  pathological  specimen  and  report  before  the  Johns  Hopkins 
Hospital  Medical  Society,  February  2,  1891. 
Johns  Hopkins  Hosp.  Bull.,  Bait.,  1891,  II,  142. 
286 


DUPLICATURE  OF  ARCH  OF  AORTA  387 

seat  of  a  saccular  aneurism  about  the  size  of  a  hen's  egg,  with  a  somewhat 
triangular  mouth  measuring  2  by  1,5  cm.  in  diameter.  The  walls  of  tlie 
opening  are  smooth  and  the  inner  surface  of  the  aneurism  only  a  little  irregu- 
lar and  rough.  The  sac  contains  fluid  and  red  freshly  coagulated  blood. 
There  are  only  a  few  scattered  patches  of  endarteritis  in  the  wall  of  the 
aneurism  and  elsewhere  in  the  course  of  the  aorta,  some  of  these  being 
atheromatous.  From  the  posterior  division  of  the  arch  are  given  off  the 
right  carotid  and  subclavian  arteries,  the  former  arising  from  the  sac  of  the 
aneurism  and  the  latter  a  short  distance  beyond  this  {i.  e.  further  from  the 
heart).  Beyond  the  aneurism  the  posterior  division  measures  3^  cm.  in 
length  and  1  cm.  in  diameter. 

The  chief  interest  in  the  specimen  is  the  duplicature  of  the  transverse  part 
of  tlie  arch  of  the  aorta.  This  congenital  anomaly,  as  well  as  others  affecting 
the  aortic  arch,  can  be  understood  only  by  a  consideration  of  the  embryologi- 
cal  development  of  the  aorta  and  its  branches,  and  from  this  point  of  view 
and  from  that  of  comparative  anatomy  these  anomalies  are  of  great  interest. 
Duplicature  of  the  transverse  arch  of  the  aorta  is  to  be  explained  by  the 
persistence  after  birth  of  conditions  belonging  to  early  foetal  life,  which 
should  have  disappeared  in  the  normal  course  of  development.  The  fourth 
right  aortic  arch  (calling  the  arch  nearest  the  heart  the  fifth)  persists 
throughout  its  course  and  constitutes  the  posterior  division  of  the  arch  in 
our  specimen.  In  normal  development  the  beginning  of  the  right  fourth 
aortic  arch  becomes  the  innominate  artery  from  which  ascends  the  right 
common  carotid,  corresponding  to  the  prolongation  of  the  right  ascending 
root  of  the  aorta  or  the  beginning  of  the  third  right  aortic  arch.  The  trans- 
verse part  of  the  right  fourth  aortic  arch  (the  right  fourth  bronchial  artery) 
becomes  the  right  subclavian,  from  which  the  vertebral  is  given  off,  and  the 
descending  part  of  the  right  fourtli  arch,  which  in  early  development  unites 
with  the  corresponding  part  of  the  left  fourth  arch  to  make  the  aorta 
descendens,  is  obliterated.  It  is  in  the  persistence  of  this  descending  part 
of  the  fourth  right  aortic  arch  that  the  abnormality  essentially  consists  by 
which  the  so-called  duplicature  of  the  arch  of  the  aorta  is  produced,  and  it 
is  interesting  to  note  that  in  the  amphibia  this  condition  is  normal,  a  right 
as  well  as  a  left  aortic  arch  existing. 

The  first  record  of  an  abnormality  in  the  human  being  similar  to  that  in 
our  specimen  appears  to  be  by  Hommel  in  1737,  but  in  Hommel's  case  both 
the  oesophagus  and  the  trachea  passed  through  the  ring  formed  by  the  an- 
terior and  the  posterior  divisions,  whereas  in  our  case  only  the  trachea 
enters  the  ring.  Since  Hommel  a  number  of  cases  of  duplicature  of  the 
aortic  arch  presenting  considerable  diversity  in  the  exact  arrangement  and 
the  origin  of  branches  in  different  cases  have  been  recorded.  I  hare  not 
found  any  case  recorded  in  which  the  posterior  division  was  the  seat  of  an 
aneurism  as  in  the  present  case. 


SUDDEN  DEATHS  FROM  CAEDIAC  DISEASE ' 

The  first  specimen  was  one  of  thrombosis  of  the  descending  branch  of  tlie 
left  coronary  artery. 

The  patient  was  a  strongly  built,  well-nourished  Gennan,  55  years  old. 
Five  years  ago,  he  had  an  attack  of  acute  articular  rheumatism,  and  had 
suffered  from  sub-acute  attacks  of  rheumatism  for  several  years.  He  had 
been  a  hard  drinker.  For  several  mouths  before  admission  to  the  hospital, 
he  had  suffered  from  pain  in  the  region  of  the  heart,  palpitation,  shortness 
of  breath  and  bloody  expectoration.  He  had  paroxysmal  attacks  of  cardiac 
dyspnoea  and  pain.    He  had  not  noticed  any  swelling  of  the  feet. 

On  admission  the  respiration  was  quiet.  The  pulse  was  72,  small  and 
regular.  The  arterial  wall  somewliat  stiff.  The  apex  beat  of  the  heart  was 
in  the  fifth  intercostal  space  below  nipple.  There  was  a  presystolic  thrill, 
and  marked  shortness  of  the  first  soimd.  A  loud  presystolic  murmur  was 
heard  at  apex.  Both  aortic  sounds  were  clear.  The  urine  contained  albu- 
men, hyaline  and  granular  casts.  Patient  was  in  the  hospital  for  four  weeks, 
during  which  he  had  occasional  paroxysmal  attacks  of  dyspnoea,  lasting  for 
an  hour  or  more.  In  the  intervals  his  condition  was  fairly  comfortable.  On 
the  morning  of  Xovember  30th,  he  was  suddenly  seized  with  pain  in  the  chest 
and  shortness  of  breath,  and  in  a  few  moments  before  any  assistance  could 
be  rendered  he  was  dead. 

At  the  autopsy  tlie  essential  lesions  were  found  in  the  heart.  The  mitral 
orifice  was  greatly  narrowed,  measuring  13x8  mm.  The  chordae  tendineae 
of  the  mitral  valve  were  thickened  and  shortened;  the  mitral  segments 
thickened  and  atheromatous,  free  from  thrombi.  The  otlier  valves  were 
normal.  Tlie  heart  was  greatly  hypertrophied  and  dilated.  The  hyper- 
trophy and  dilatation  of  the  left  auricle  were  most  extreme,  its  wall  meas- 
uring in  places  6  mm.  in  thickness.  The  wall  of  the  left  ventricle  measured 
23  mm.  and  that  of  the  right  ventricle  5  mm.  in  thickness.  The  heart  muscle 
was  firm  and  of  a  dark  reddish-bro\vni  color.  On  microscopical  examination 
it  ])rescnted  slight  fatty  degeneration. 

The  coronary  arteries  were  markedly  atheromatous,  their  walls  l)oing 
irregularly  thickened  and  presenting  on  the  inner  surface  irregular,  elevated, 
opaque,  yellowish  white  patches.  The  left  coronary  artery  contained,  3  cm. 
from  its  origin,  a  fresh  dark  red,  almost  black,  thrombus,  adherent  to  an 
atheromatous  plaque,  and  about  one-half  centimeter  in  length.  This 
thrombus  completely  occluded  the  lumen  of  the  artery  at  this  point.  It  was 
situated  in  the  descending  or  vertical  branch  of  the  left  coronary  artery. 

'  Presentation  of  pathological  specimens  and  report  before  the  Johns  Hopkins 
Hospital  Medical  Society,  December  2,  1889. 

Johns  Hopkins  Hosp.  Bull.,  Bait.,  1889-90,  I,  34-35. 

288 


STJDDEX  DEATHS  FROM  CARDIAC  DISEASE  289 

The  aorta  throughout  its  entire  extent  appeared  thickened,  dilated,  and 
presented  numerous  elevated  atheromatous  patches. 

The  lungs,  liver,  spleen,  and  kidney  presented  marked  chronic  passive  con- 
gestion. The  spleen  and  kidney  contained  the  scars  of  old  infarctions.  The 
large  and  small  bronchi  contained  niuco-pus. 

There  was  an  area  of  old  softening  involving  the  cortex  of  the  left  second 
and  third  frontal  convolutions  near  the  anterior  central  convolution  and  the 
adjacent  part  of  the  island  of  Reil. 

The  chief  interest  of  the  case  is  the  explanation  of  the  sudden  death  of 
the  patient.  This  is  imdoubtedly  referable  to  the  fresh  thrombus  which  was 
found  attached  to  an  atheromatous  patch  in  the  main  branch  of  the  left 
coronary  artery.  Although  marked  atheromatous  disease  of  the  coronary 
arteries  existed,  the  circulation  in  tliese  vessels  had  not  been  sufficiently 
impeded  to  give  rise  to  fibroid  patches  in  the  myocardium.  The  appearance 
of  the  thrombus  and  the  absence  of  infarction  or  anaimic  necrosis  of  the 
heart  muscle,  are  evidence  that  the  clot  must  have  been  of  recent  formation. 
The  cause  of  the  thrombosis  was  doubtless  the  irregular  atheromatous  pro- 
jecting plaque  to  which  the  thrombus  was  adherent.  As  is  well  known,  dis- 
eases obstructing  the  circulation  of  blood  through  the  coronary  arteries, 
such  as  arterio-sclerosis,  thrombosis,  embolism  of  these  vessels,  are  among 
the  most  frequent  causes  of  sudden  death. 

The  second  specimen  was  one  of  complete  occlusion  of  the  mouth  of  the 
right  coronary  artery. 

The  patient,  a  negro  36  years  old,  about  six  months  before  admission  to 
the  hospital  began  to  suffer  from  shortness  of  breath  on  exertion,  and  palpita- 
tion of  the  heart.  (Edema  of  the  lower  extremities  appeared,  but  he  was 
unable  to  do  the  work  of  a  laboring  man  until  six  weeks  before  admission. 
Upon  admission  there  were  observed  severe  dyspnoea,  general  anasarca,  pul- 
sation of  the  veins,  increased  area  of  cardiac  dulness,  the  apex  beat  being  in 
sixth  intercostal  space  in  middle  line  of  axilla,  and  diastolic  and  systolic 
murmurs  heard  most  distinctly  over  base  of  heart.  The  urine  was  scant}', 
specific  gravity  1010  and  contained  granular  and  hyaline  casts,  and  some 
red  blood  corpuscles  and  pus  cells.  For  a  time  he  improved  under  treatment 
but  a  few  hours  before  death  his  pulse  became  verj'  irregular,  small,  feeble 
and  compressible,  and  he  died  somewhat  suddenly. 

At  the  autopsy  the  heart  was  found  greatly  hypertrophicd  and  dilated, 
the  left  ventricle  being  14  and  the  right  12  cm.  long.  The  heart  weighed  858 
grammes.  The  thickness  of  the  wall  of  the  left  ventricle  was  25  mm.;  that 
or  right  ventricle  9  mm.  The  segments  of  the  aortic  valve  were  much  thick- 
ened, roughened,  retracted,  and  adherent  to  each  other.  The  muscular  sub- 
stance of  the  left  ventricle  presented  several  grayish,  irregular  fibroid  patches 
taking  the  place  of  the  muscular  tissue.  The  papillary  muscles  were  ex- 
tensively fibroid.  The  aorta  for  a  distance  of  4  cm.  above  the  valves  pre- 
sented a  remarkable  nodular  thickening  of  the  intima  resulting  from  arte- 
rio-sclerosis.   There  were  a  few  small  nodules  of  calcification,  but  most  of 


290  SUDDEN  DEATHS  FROM  CARDIAC  DISEASE 

the  endarteritis  was  gelatinous  and  fresh  in  appearance.  Beyond  this  cir- 
cumscribed zone  of  arterio-sclerosis  the  aorta  presented  only  a  few  small 
patches  of  atheroma,  and  in  general  the  arteries  of  the  body  were  but  slightly 
atheromatous.  The  coronary  arteries  of  the  heart,  however,  presented  a 
number  of  atheromatous  patches.  The  most  interesting  feature  of  the  case 
was  the  complete  obliteration  of  the  mouth  of  the  right  coronary  artery. 
This  mouth  was  involved  in  the  extensive  fibrous  endarteritis  affecting  the 
aorta  just  above  the  valves,  so  that  it  was  impossible  to  discover  any  opening 
from  the  aorta  into  the  right  coronary  artery.  This  artery,  however,  was 
present  in  its  normal  situation  and  distribution  and  its  lumen,  apparently 
intact,  could  be  traced  nearly  to  the  origin,  where  even  the  finest  probe  could 
not  be  made  to  pass  from  the  lumen  into  the  aorta.  The  left  coronary  artery 
apptmred  dilated  but  no  large  branch  of  anastomosis,  connecting  the  left  and 
the  right  coronary  arteries,  could  be  discovered.  The  riglit  coronary  must 
have  been  supplied  with  blood  from  the  left  artery. 

The  muscular  substance  of  the  heart,  save  the  fibroid  growth,  was  normal 
in  appearance  and  free  from  fatty  degeneration. 

The  organs  of  the  body  showed  evidences  of  chronic  venous  congestion, 
and  in  the  right  kidney  and  ureter  were  fresii  tubercle  deposits  associated 
with  caseous  tuberculosis  of  the  prostate  gland. 

The  case  is  interesting  as  showing  complete  obliteration  of  the  right 
coronary  artery  at  its  origin  by  arterio-sclerosis  of  tlie  aorta.  NotwiUi- 
standing  the  absence  of  any  large  anastomosing  branches  between  the  left 
and  the  right  coronary  arteries,  sufficient  blood  reached  the  regions  of  the 
heart,  supplied  by  the  right  coronary,  to  nourish  these  parts  and  to  prevent 
any  fatty  degeneration.  The  fibroid  patches  were  chiefly,  in  parts,  supplied 
by  the  left  coronary  artery. 

The  third  specimen  was  one  of  extreme  atheroma  and  thrombosis  of  the 
coronary  arteries  with  multiple  white  infarctions  in  wall  of  left  ventricle. 

The  patient  was  a  woman  67  years  old  who,  for  twenty  years  preceding 
death,  had  complained  of  occasional  attacks  of  pain  in  the  region  of  the 
heart.  During  the  last  three  months  of  life  she  had  suft'ered  from  par- 
oxysms of  typical  iuigina  pectoris,  from  attacks  of  extreme  dyspncea,  from 
great  restlessness  and  some  mentiil  disorder.  The  pulse  was  irregular  and 
feel)le.  The  heart  sounds  ap[)cared  to  be  normal.  Some  (vdcnia  of  tiie  lower 
extremities  developed.  ^I'lie  urine  contained  a  small  quantity  of  albumen  and 
a  few  hyaline  casts.  During  the  last  few  days  of  life  she  suffered  from  great 
pain  and  distress  in  the  region  of  the  heart,  and  she  expectorated  small  dark 
clots  of  blood. 

At  the  post-mortem  examination  the  heart  was  only  moderately  enlarged, 
and  this  enlargement  was  due  chietly  to  a  considerable  deposit  of  adipose 
tissue  l)eneath  the  epicardiiim.  Tlu^rt'  was  general  obesity  of  the  body.  The 
left  ventricle,  at  about  its  middle,  measured  1  cm.  in  thickness.  Below  tliis 
it  l)<3came  gradually  thinner,  and  at  tiio  apex  measured  only  4  mm.  in  thick- 
ness, of  which  one-half  wi\s  fat.  The  average  thickness  of  the  right  ven- 
tricular wall  was  ')  to  6  mm.,  of  which  only  2  nun.  represented  muscular 
tissue,  the  rest  being  fat.     The  right  cavities  of  the  heart  were  distended 


STTDDEN  DEATHS  FROM  CARDIAC  DISEASE  291 

with  coagulated  blood,  chiefly  cruor  clots,  but  some  decolorized;  but  little 
blood  was  found  in  the  left  ventricle.  The  aortic  valves  and  the  aortic  seg- 
ment of  the  mitral  valve  presented  several  yellowish,  fatty  and  atherom- 
atous patches,  but  the  edges  of  the  valves  were  delicate  and  there  were  no 
evidences  of  any  change  which  would  interfere  with  the  functions  of  the 
valves.  There  were  numerous  ante-mortem  thrombi  attached  to  the  inner 
surface  of  the  left  and  of  the  right  ventricles  in  their  lower  halves,  and 
filling  the  appendices  of  the  auricles.  Many  of  these  thrombi  were  globular 
and  had  undergone  central  softening.  In  the  left  ventricle  they  were  con- 
tinuous with  areas  of  necrosis  in  the  ventricular  wall,  and  it  was  not  always 
possible  to  recognize  the  line  of  separation  between  tlie  thrombus  and  the 
necrotic  wall. 

The  coronary  arteries  were  extremely  atheromatous,  standing  out  as  rigid 
tortuous  calcified  vessels  with  atheromatous  projections  on  their  inner  sur- 
face. Even  the  small  branches  could  be  traced  through  the  heart  wall  by 
means  of  the  calcified  beaded  thickenins-s  which  they  presented.  Both 
coronary  arteries  were  greatly  narrowed  by  atheromatous  degeneration  near 
their  origin.  In  many  places  grayish-red  thrombi  were  present  in  the 
branches  of  the  left  coronary  artery,  sometimes  parietal  and  sometimes, 
especially  in  the  smaller  branches,  occluding.  They  occurred  in  situations 
where  there  was  well  marked  atheroma.  The  left  coronary^  artery  was  more 
extensively  diseased  than  the  right. 

A  large  part  of  the  wall  of  the  left  ventricle  was  the  seat  of  white  infarc- 
tion or  anaemic  necrosis.  These  areas  of  coagulation-necrosis  had  an  opaque, 
yellowish-white  color,  a  firm  consistence  and  well  defined  but  irregular 
margins.  They  projected  on  the  cut  surface  above  the  level  of  the  sur- 
rounding muscle  which,  in  the  immediate  neighborhood  of  tlie  infarctions, 
appeared  depressed,  gelatinous,  reddish  in  color  and  soft.  The  areas  of 
necrosis  were  found  only  in  the  wall  of  the  left  ventricle  and  in  the  septum 
ventriculorum ;  they  occurred  chiefly  in  the  part  of  the  myocardixmi  nearest 
the  endocardium,  and  usually,  but  not  in  all  cases,  reached  the  endocardium. 
Sometimes  they  had  more  or  less  of  a  wedge-shape,  but  generally  they  were 
irregular  in  contour.  They  varied  from  2  to  6  mm.  in  thickness,  and 
appeared  to  have  coalesced  with  each  other  so  as  to  form  a  nearly  continuous 
band  of  coagulation-necrosis  in  the  lower  part  of  the  left  ventricle.  They 
occurred  both  on  the  anterior  and  on  the  posterior  wall  of  the  ventricle  as 
well  as  in  the  septum.  The  papillary  muscles  of  the  left  ventricle  were 
affected  with  coagulation-necrosis  throughout  nearly  their  entire  extent. 

In  addition  to  the  infarctions  the  myocardimn  of  both  ventricles  was 
affected  by  marked  fatty  degeneration,  and  presented  a  characteristic  faded- 
leaf  mottling  as  seen  through  the  endocardium. 

The  lungs  were  the  seat  of  chronic  passive  congestion,  of  general  bron- 
chitis, of  oedema ;  and  in  the  right  lung  were  many  firm,  black,  large,  wedge- 
shaped  hemorrhagic  infarctions. 

The  liver,  spleen,  kidneys  and  stomach  presented  the  usual  appearances  of 
chronic  passive  congestion. 

The  aorta  and  its  principal  l)ranches  were  the  seat  of  marked  arterio- 
sclerosis, presenting  both  gelatinous,  elevated,  fresh  plaques  and  old  calcified 
plates. 


292  SUDDEN  DEATHS  FROM  CARDIAC  DISEASE 

Microscopical  sections  were  exhibited  showing  the  appearances  of  the  in- 
farctions in  the  heart  wall.  In  the  necrotic  areas  the  muscular  fibres  were 
entirely  devoid  of  nuclei,  and  presented  a  homogeneous,  hyaline  or  indis- 
tinctly striated  appearance.  In  the  edge  of  the  infarction  were  accumulated 
between  tlie  muscular  fibres  masses  of  small  irregular  particles  presenting 
a  nuclear  stain  and  doubtless  the  result  of  nuclear  fragmentation.  Beyond 
this  zone  was  found  an  accumulation  of  leucocytes  between  the  fibres,  and  a 
large  number  of  red  blood  corpuscles.  Mixed  thrombi,  rich  in  fibrin,  leuco- 
cytes and  blood-plates  appeared  on  the  sections  attached  to  the  necrotic 
endocardium.    Such  thrombi,  however,  were  not  limited  to  the  necrotic  areas. 

In  addition  to  the  recent  infarctions,  the  muscular  wall  of  the  left  ven- 
tricle contained  a  number  of  old  fibroid  patches.  Along  the  borders  of  some 
of  the  infarctions  genuine  granulation  tissue,  rich  in  cells  and  in  blood- 
vessels was  present. 


AN  EXPERI]\IENTAL  STUDY  OF  GLOMERULO-NEPHRITIS  ' 

Of  the  various  processes  which  make  up  the  pathological  anatomy  of 
Bright's  disease,  perhaps  the  two  which  at  present  awaken  the  greatest  in- 
terest and  the  study  of  which  promises  the  most  fruitful  results,  are  the 
changes  which  take  place  in  tlie  glomeruli  and  atrophy  and  necrosis  of  the 
epithelial  cells  in  relation  to  interstitial  changes.  Not  tliat  by  any  means 
unanimity  of  opinion  has  been  reached  regarding  other  fundamental  ques- 
tions involving  the  relationship  between  tlie  glandular,  the  interstitial,  and 
the  vascular  lesions  of  Bright's  disease,  but  the  two  processes  named  have 
acquired  especial  prominence  within  the  last  few  years  by  the  recognition  of 
their  frequency  and  importance. 

Alterations  of  the  Malpigliian  bodies,  with  which  alone  the  present  paper 
is  concerned,  were  described  with  much  accuracy  and  fulness  by  Beer  in  his 
excellent  treatise  on  "  The  Connective  Tissue  of  the  Human  Kidney  in  the 
Healthy  and  the  Diseased  State,"  published  in  1859,  but  until  recently  little 
attention  was  paid  to  his  observations.  Klebs,  by  his  description  in  1876 
of  the  lesion  to  which  he  gave  the  name  of  glomerulo-nephritis,  incited  re- 
newed investigation  of  this  subject.  During  the  last  ten  years  procevSses 
embraced  under  the  name  of  glomerulo-nephritis  have  been  studied  by  Cornil, 
Hortoles,  Friedlander,  Ribbert,  Nauwerck,  and  many  others,  but  we  owe  to 
Langhans  the  most  extensive  and  accurate  observations  on  tliis  subject. 

A  comparison  of  the  statements  of  different  writers  concerning  glomerulo- 
nephritis will  show  a  wide  diversity  of  views,  not  only  as  to  the  interpreta- 
tion of  tlie  facts  observed  but  as  to  the  facts  themselves.  Without  attempt- 
ing a  critical  analysis  of  these  divergent  views,  the  following  summary  of 
some  of  the  conclusions  of  different  observers  will  show  this  to  be  true. 

At  present  little  or  no  credence  is  given  to  Kleb's  belief  that  the  essential 
lesion  of  glomerulo-nephritis  is  proliferation  of  connective  tissue  cells  which 
he  supposed  to  exist  between  the  capillaries  of  the  glomerulus,  although  this 
belief  still  receives  some  support  from  the  conception  of  Hortoles,  and  of 
Cornil  and  Brault,  as  to  the  connective-tissue  nature  of  these  intercapillary 
cells. 

Langhans,  in  his  publication  in  18 T 9,  dwelt  especially  upon  swelling, 
proliferation,  and  desquamation  of  the  epithelial  cells  both  of  the  glomerulus 

^  Presented  at  the  first  meeting  of  the  Association  of  American  Physicians  and 
Surgeons,  Army  Medical  Museum,  Washington,  D.  C,  June  18,  1886. 
Tr.  Ass.  Am.  Pliysicians,  Phila.,  1886,  I,  171-183. 

293 


294  EXPERIMENTAL  STUDY  OF 

and  of  Bowman's  capsule;  whereas  in  his  last  article,  published  in  1885,  he 
regards  swelling  and  proliferation  of  the  endothelium  lining  the  glomerular 
capillaries  as  the  primary  and  essential  lesion  of  glomerulo-nephritis,  as 
indeed  of  all  forms  of  acute  nephritis.  Similar  views  are  held  by  Fried- 
lander  and  by  Nauwerck. 

Eibbert  considers  that  the  only  changes  are  swelling  and  desquamation 
of  the  glomerular  and  capsular  epithelium,  changes  whicii  he  regards  as 
essential  to  all  forms  of  acute  and  chronic  Bright's  disease  and  as  answerable 
for  many  of  the  symptoms.  He,  as  well  as  Hortoles  and  Cornil,  refers  the 
appearances  described  by  Langhans  as  proliferation  of  the  capillary  endo- 
thelium to  an  accumulation  of  white  blood-corpuscles  in  tlie  capillaries. 

Cornil  and  Brault  assign  an  insignificant  and  inconstant  role  to  changes 
in  the  epithelium  of  the  glomerulus  and  of  its  capsule,  and  find  the  funda- 
mental lesion  of  acute  glomerulo-nephritis  to  be  an  exudation  from  tlie 
glomerular  capillaries  of  inflammatory  products  composed  of  white  blood- 
corpuscles,  red  blood-corpuscles,  and  an  albuminous  fluid. 

On  the  other  hand,  Hortoles  and  Ribbert  deny  altogether  the  occurrence 
of  emigration  through  the  glomerular  capillaries,  basing  this  view  on  the 
failure  to  find  leucocytes  in  the  capsular  space  when  their  presence  cannot  be 
explained  by  emigration  from  capillaries  adjacent  to  Bowman's  capsule. 
In  further  support  of  their  view  they  urge  the  peculiar  structure  of  the  capil- 
laries of  the  glomerulus. 

But  it  is  not  necessary  to  consume  time  in  a  further  enumeration  of  the 
different  views  which  are  held  upon  this  subject.  Enough  have  been  cited 
to  show  that  there  is  room  for  much  more  investigation,  as  well  as  to  bring 
out  some  of  the  leading  points  which  require  further  study. 

In  the  expectation  that  light  might  be  thrown  upon  some  of  these  doubtful 
points  by  experiments  upon  animals,  I  have  made  a  study  of  the  nephritis 
produced  by  acute  cantharidin  poisoning  with  especial  reference  to  the  altera- 
tions induced  in  the  Malpigliian  bodies.  I  was  led  to  select  cantharidin 
because  several  experimenters  with  this  substance  have  described  in  can- 
tharidin nephritis  notable  changes  in  the  Malpighian  bodies,  and  because 
Cornil  bases  his  description  of  acute  glomerulo-nephritis  chiefly  upon  ob- 
servations of  the  kidneys  of  rabbits  poisoned  by  cantharidin. 

My  experiments,  which  have  not  yet  reached  their  completion,  were  made 
upon  white  rats  and  upon  rabbits.  A  concentrated  solution  of  cantharidin 
in  acetic  ether  was  used.  I  injected,  subcutaneously,  in  rabbits  usually  from 
one-half  to  one  centigramme  of  cantharidin,  and  in  rats  from  one  to  three 
milligrammes.  When  a  number  of  injections  were  made  upon  successive 
days  smaller  doses  were  used.  The  number  of  injections  did  not  exceed  five, 
and  usually  not  more  than  two  or  three. 


GLOMERULO-NEPHRITIS  295 

After  the  injection  of  a  toxic  dose  tlie  urine  becomes  diminished  and 
finally  suppressed;  it  contains  albumen,  hyaline  casts,  and  a  large  number 
of  leucocytes  and  red  blood-corpuscles.  The  kidneys  appear  swollen,  con- 
gested, and  more  succulent  than  normal. 

The  microscopical  appearances  in  the  rat's  kidney  will  be  first  described. 
Here  and  tliere  foci  of  infiltration  witli  small  round  cells,  doubtless  emi- 
grated white  blood-corpuscles,  can  be  found.  They  are  most  common  around 
the  veins  at  the  base  of  the  pyramid.  They  are  often  but  not  constantly 
present. 

The  epithelium  of  the  convoluted  tubes  is  in  places  normal  in  appearance, 
in  other  places  it  is  swollen,  and  often  the  inner  part  of  the  epithelial  cells 
is  broken  off  and  appears  as  a  granular  mass  in  the  limien  of  tlie  tubes. 
Sometimes  a  large  number  of  epithelial  cells  are  devoid  of  nuclei,  and  have 
apparently  undergone  coagulation  necrosis.  In  general,  the  convoluted 
tubes  are  wider  than  normal. 

The  most  marked  changes  are  to  be  found  in  the  Malpighian  bodies.  In 
by  far  the  greater  number  of  these  bodies  tliere  is  between  the  glomerulus 
and  Bowman's  capsule  a  wide  space  partly  or  wholly  filled  with  cells  and 
granular  material.  These  cells  may  be  round  or  oval,  but  they  are  usually 
polyhedrical  in  shape.  They  are  much  larger  than  white  blood-corpuscles, 
have  granular  protoplasm,  and  oval,  vesicular  nuclei.  They  are  frequently 
arranged  as  a  crescentic  mass  around  the  glomerulus. 

Evidently  we  have  here  appearances  such  as  have  been  often  described  as 
glomerulo-nephritis  in  the  human  kidney,  and  naturally  one  seeks  for  the 
same  origin  of  these  cells  as  that  assigned  for  the  cells  similarly  situated  in 
human  glomerulo-nephritis,  namely,  swelling  and  desquamation,  and  possi- 
bly proliferation  of  either  the  capsular  or  the  glomerular  epithelium. 

The  microscopical  appearances  in  the  rat's  kidney,  however,  do  not  admit 
of  this  explanation.  The  epithelium  lining  the  capsule  of  Bowman  is  often 
intact,  and  can  be  traced  in  its  normal  situation  and  with  its  nonnal  appear- 
ances around  the  mass  of  cells  occupying  the  capsular  space.  The  glomerular 
epithelium  may  also  preserve  its  normal  position ;  more  frequently  it  is  some- 
what swollen  and  granular,  ajid  it  may  desquamate.  Such  desquamated 
glomerular  epithelial  cells  may  be  mingled  with  the  cells  free  in  the  capsular 
space,  but  there  are  no  appearances  which  justify  the  derivation  of  the 
majority  of  these  latter  cells  from  the  epithelium  of  the  glomerulus. 

Both  Cornil  and  Eliaschoff,  whose  descriptions  of  cantharidin  nephritis 
are  the  best  which  I  have  found,  and  who  experimented  on  rabbits,  also  came 
to  the  conclusion  that  the  cells  occupying  the  capsular  space  cannot  be  de- 
rived from  either  the  epithelium  of  Bowman's  capsule  or  that  of  the  glomer- 
ulus. They  argue  that  there  remains  but  one  other  possible  source,  namely, 
emigration  of  white  blood-corpuscles  from  the  glomerular  capillaries.    They 


296  EXPERIMENTAL  STUDY  OF 

therefore  consider  the  cells  in  question  as  white  blood-corpuscles,  of  which 
the  cell  bodies  and  the  nuclei  are  greatly  swollen  and  altered  by  the  action  of 
the  cantharidin  or  of  the  urine. 

So  far  as  the  rat's  kidney  is  concerned,  this  explanation  of  Comil  and  of 
Eliaschoff  cannot  be  admitted.  These  authors  are  in  error  in  supposing  that 
the  cells  occupying  the  capsular  space,  if  not  originating  from  the  capsular 
or  glomerular  epithelium,  must  come  from  the  capillaries.  These  cells  may 
be  derived  also  from  the  convoluted  tubes  in  immediate  communication  with 
the  Malpighian  bodies,  and  that  this  is  their  origin,  at  least  in  part,  in  the 
cantharidin  nephritis  of  rats  can  be  proven,  I  believe,  beyond  question.  The 
cells  in  the  capsular  space  are  identical  in  appearance  with  the  epithelial 
cells  of  the  adjacent  convoluted  tubes.  The  appearances  presented  on  sec- 
tions which  show  the  communication  between  the  capsular  space  and  the 
corresponding  convoluted  tube  hardly  admit  of  any  other  interpretation  than 
that  which  I  have  given.  Here  it  can  be  seen  that  the  mass  of  cells  in  the 
capsular  space  is  in  direct  connection  with  the  epithelium  of  the  convoluted 
tube,  and,  what  is  especially  demonstrative,  there  can  frequently  be  found 
in  this  mass  a  group  of  cells  arranged  regularly  in  the  form  of  a  ring  with 
a  central  space,  just  hke  the  epithelium  of  a  uriniferous  tube.  Without  the 
explanation  given,  such  an  arrangement  of  the  cells  is,  of  course,  very 
puzzling,  especially  when  the  Malpighian  body  is  cut  so  as  not  to  show  the 
connection  with  the  tube.  The  appearance  is  as  if  the  epithelial  cells  lining 
the  mouth  of  the  uriniferous  tube  (or  the  neck  of  the  capsule),  together  with 
the  cells  immediately  adjacent,  had  been  pushed  mechanically  into  the 
capsular  space.  A  similarity  in  appearance  between  the  cells  accumulated 
in  the  capsular  space  and  the  epithelial  cells  of  the  convoluted  tubes,  might 
be  explained  by  the  fact  that  under  normal  conditions  the  epithelium  of  the 
convoluted  tubes  may  extend  for  a  variable  distance  along  Bowman's  capsule. 
Sucli  an  extension  of  the  tubal  epithelium  to  the  capsule  is  not  particularly 
noticeable  in  the  rat's  kidney,  and  cannot  be  adduced  to  explain  the  peculiar 
appearances  described. 

Obsen-ations  concerning  the  passage  of  epithelial  cells  from  the  con- 
voluted tubes  into  the  capsular  space,  have  been  made  by  Kolliker  *  and  by 
Argutinski.*  While  discussing  the  nature  of  the  normal  glomerular  epi- 
thelium, Kolliker  says: 

"  In  hardened  kidneys  the  epithelium  of  the  c»onvoluted  tubes  is  not  infre- 
quently pressed  up  into  the  capsules,  so  that  in  many  cases  a  membranous 
layer  is  fonned  which  is  arranged  like  a  funnel  around  one  end  of  the 
glomerulus." 

'  Kolliker,  Handb.  d.  Gewebelehre,  Leipzig.  1867.  p.  504. 

'  Argutinski.  Beitrage  zur  Normalen  und  Pathologlschen  Histologie  der  NIere, 
p.  18.    Inaug.  Diss.    Halle.  1877. 


GLOMERTJLO-NEPHRITIS  297 

Kolliker^s  observations  relate,  therefore,  to  artefacts  produced  by  the 
action  of  the  hardening  fluid.  In  the  cases  of  cantharidin  nephritis  which  I 
have  studied,  the  accumulation  of  tubal  epitlielium  within  the  capsules  can- 
not be  regarded  as  an  artefact,  for  the  same  appearances  can  be  seen  in  sec- 
tions of  the  fresh  kidney  as  in  sections  of  kidneys  hardened  in  Miiller's  fluid, 
chromic  acid,  Flemming's  solution,  picric  acid,  osmic  acid,  and  alcohol. 
The  change  is,  therefore,  one  which  occurs  during  the  life  of  the  animal. 
The  same  appearances  in  the  Malpighian  bodies  which  I  have  observed  in 
the  cantharidin  nephritis  of  white  rats,  have  been  described  and  figured 
by  Argutinski  as  occurring  in  the  embolic  infarctions  experimentally  pro- 
duced in  dogs  by  injecting  into  the  renal  arteries  plugs  of  wax.  He  also 
speaks  of  the  possibility  of  producing  the  same  change  by  forcible  injection 
of  fluids  into  the  renal  bloodvessels.  He  therefore  assigns  as  the  cause  of 
this  phenomenon  the  pressure  exerted  by  dilated  bloodvessels  ujwn  the 
convoluted  tubes,  whereby  the  protoplasmatic  contents  of  the  latter  are  forced 
upward  into  the  capsular  spaces. 

The  following  are  among  the  factors  which  may  be  adduced  to  explain  the 
mechanism  by  which  the  cells  in  cantharidin  nephritis  make  their  way  from 
the  convoluted  tubes  into  the  capsular  spaces :  Obstruction  of  tlie  uriniferous 
tubes,  both  in  the  cortex  and  in  the  pyramid,  by  desquamated  and  by  necrotic 
epithelial  cells,  and  by  hemorrhages  within  the  tubes,  pressure  upon  the 
tubes  from  without  by  congested  bloodvessels  and  by  transuded  serum,  and 
cessation  of  the  excretion  of  urine  from  the  glomeruli.  In  consideration  of 
these  alterations  in  the  kidney,  it  is  comprehensible  that  swollen  and  des- 
quamated epithelial  cells  in  the  beginning  of  a  convoluted  tube  might  find 
toward  the  capsular  space  the  direction  of  least  resistance. 

There  is,  of  course,  no  propriety  in  designating  as  glomerulo-nephritis  the 
changes  in  the  Malpighian  bodies  of  the  rat's  kidney  which  have  been  de- 
scribed. The  t^rm  glomerulo-nephritis,  however,  is  one  which  is  used  with 
much  latitude  of  significance,  and  embraces  nearly  all  of  the  changes  ob- 
served in  acute  nephritis  in  the  Malpighian  bodies  and  a  large  number  of 
those  found  in  chronic  nephritis.  Many  of  these  changes  are  not  proven  to 
be  inflammatory. 

I  am  not  able  to  say  whether  a  process  similar  to  that  which  I  have  found 
in  the  Malpighian  bodies  of  the  kidney  of  the  rat  poisoned  by  cantharidin, 
occurs  also  in  the  nephritis  of  other  animals  and  of  man.  In  the  acute  can- 
tharidin nephritis  of  rabbits  the  capsular  spaces  also  contain  granular  ma- 
terial and  cells,  but  the  cells  do  not  form  such  compact  masses  as  in  the 
rat's  kidney,  and  more  frequently  undergo  necrosis.  I  have  not  been  able 
as  yet  to  reach  a  positive  conclusion  as  to  the  origin  of  these  cells.  To  the 
descriptions  which  have  been  repeatedly  given  of  the  cantharidin  nephritis 
22 


298  EXPERIMENTAL  STUDY  OF 

of  rabbit'^,  I  have  to  add  the  almost  constant  occurrence  of  necrosis  of  epithe- 
lial cells  in  certain  tubes  occupying  the  boundary  zone  of  the  pyramid  and 
the  medullary  rays.  These  tubes  appear  to  be  terminal  portions  of  the 
proximal  convoluted  tubes  (Endstiickchen,  spiral  tubes).  Hemorrhages 
witliin  the  tubes,  particularly  those  of  the  pyramid,  are  not  infrequent. 

In  human  glomerulo-nephritis  one  is  not  generally  at  a  loss  to  account 
for  the  crescentic  mass  of  cells  which  frequently  occupies  the  capsular  space. 
The  presence  of  these  cells  is  accompanied  with  sweUiug  and  desquamation 
of  either  tlie  glomerular  or  the  capsular  epithelium,  usually  of  both,  and 
these  changes  explain  the  accumulation  of  cells  in  the  capsular  space. 

One  of  tlie  leading  objects  in  making  these  experiments  on  cantharidin 
nephritis  was  to  determine  whether  changes  were  thereby  produced  in  the 
glomerular  capillaries.  FriedlJinder,  Nauwerck,  and  Langhans  have  called 
attention  to  the  accumulation  of  cells  in  the  interior  of  the  glomerular  capil- 
laries as  a  frequent  and  important  lesion  of  acute  and  of  chronic  nephritis. 
These  cells  they  regard,  for  the  most  part,  as  prohferated  capillary  endo- 
thelial cells.  Previous  experimenters  on  nephritis  may  no  mention  of  altera- 
tions in  tlie  glomerular  capillaries,  so  far  as  I  have  been  able  to  learn. 

The  technical  difficulties  attending  the  microscopical  investigation  of  the 
glomerular  capillaries  are  considerable.  It  is  often  desirable,  as  recom- 
mended by  Langhans,  that  these  capillaries  should  be  injected  with  color- 
less gelatine,  although  when  they  are  widely  distended  with  cells,  as  in  some 
instances  of  Bright's  disease,  such  a  procedure  is  not  necessary.  The  sections 
of  the  glomeruli  must  be  extremely  thin,  and  this  is  best  accomplished  by 
embedding  pieces  of  the  kidney  either  in  celloidin  or  in  paraffin,  in  the 
latter  ca.^e  cutting  the  sections,  of  course,  with  the  drj'  razor  placed  at  right 
angles  to  the  specimen. 

In  some  cases  of  cantharidin  nephritis  no  changes  can  be  detected  in 
the  glomerular  capillaries;  in  some  instances,  however,  especially  in  tlie 
rabbit,  these  capillaries  contain  a  large  number  of  small,  darkly  staining 
nuclei,  readily  distinguished  from  the  larger  and  paler  nuclei  of  the 
glomerular  epithelium.  These  nuclei  belong  for  the  most  part  to  spherical, 
granular  cells,  which  I  am  inclined  to  interpret  as  white  blood-corpuscles. 
Positive  evidences  of  proliferation  of  the  capillary  endothelium  could  not  be 
found.  Changes  in  the  capillaries  comparable  in  degree  to  those  observed  in 
many  cases  of  nephritis  in  human  beings,  I  have  not  ix^en  able  to  find  in 
experimental  cantharidin  nephritis. 

The  occlusion  of  the  glomerular  capillaries  in  acute  and  chronic  Bright's 
disease  by  granular  material  and  cells,  has  been  most  fully  described  in  all 
of  its  histological  details  by  Langhans.  My  own  studies  of  human  kidneys 
are  essentially  confirmatory  of  Langhans's  descriptions. 


GLOMERULO-NEPHKITIS  299 

Swelling  of  tlie  endothelium,  and  accumulation  of  cells  in  the  glomerular 
capillaries,  are  nearly  constant  lesions  in  acute  scarlatinal  nephritis.  These 
changes  in  the  capillaries  may  be  the  only  marked  lesions  in  the  kidney, 
although,  as  a  rule,  there  is  more  or  less  accumulation  of  lymphoid  cells  in 
the  interstitial  tissue.  I  have  observed  similar  accumulation  of  cells  in  the 
glomeruhu'  capillaries  in  acute  Bright's  disease  complicating  typhoid  fever, 
and  in  a  number  of  cases  of  chronic  Bright's  disease.  The  changes  in  tlie 
capillaries  are  usually  accompanied  by  other  lesions  of  diffuse  nephritis. 

I  would,  however,  call  especial  attention  to  certain  cases  of  Bright's 
disease  which  usually  pursue  a  subacute  course,  in  which  the  accumulation 
of  cells  in  the  capillaries  of  the  glomerulus  is  the  predominant,  and  some- 
times tlie  only  evident  lesion.  The  following  case  may  serve  as  an  illustra- 
tion. 

The  patient,  who  had  had  malaria,  was  the  subject  for  two  months  of 
anasarca.  The  urine  was  scanty,  albuminous,  and  contained  casts.  Death 
resulted  from  ura-mic  convulsions.  At  the  autopsy  tliere  was  found  malarial 
pigmentation  of  the  spleen  and  other  organs,  the  heart  was  considerably 
hypertrophied,  and  the  kidneys  were  large,  the  surface  smooth,  the  capsule 
non-adherent,  and  the  cortex  swollen.  The  Malpighian  bodies  were  large 
and  pale.  Upon  microscopical  examination  of  the  kidneys,  with  the  excep- 
tion of  the  change  about  to  be  described,  there  was  very  little  abnormal. 
The  epithelial  cells  were  normal.  Only  after  careful  search  could  a  few 
patches  of  infiltration  with  lymphoid  cells  be  discovered.  The  Malpighian 
bodies  were  rich  in  nuclei.  The  glomeruli  filled  completely  the  space  en- 
closed by  Bowman's  capsule.  The  case  seemed  a  puzzling  one,  until  after 
tlie  examination  of  very  thin  sections  it  was  found  that  almost  everywhere 
the  glomerular  capillaries  were  dilated,  and  contained  a  large  number  of 
cells,  partly  resembling  white  blood-corpuscles,  but  mostly  larger,  and  of  an 
endothelioid  type. 

Probably  many  pathologists  have  met  with  kidneys  in  which  tlie  lesions 
seemed  entirely  inadequate  to  explain  the  symptoms.  Doubtless  a  certain 
number  of  these  obscure  cases  belong  to  the  class  just  described.  It  certainly 
is  important  that  a  careful  examination  be  made  of  the  condition  of  the 
glomerular  capillaries. 

It  is  not  necessary  to  dwell  upon  the  importance  which  attaches  to  the 
lesions  of  the  glomerular  capillaries  which  have  been  described.  When  one 
considers  the  physiological  functions  of  the  glomeruli,  it  is  difficult  to  think 
of  any  lesion  of  tlie  kidney  more  destructive  of  its  functions  than  the  occlu- 
sion of  the  capillaries  of  the  glomenilus.  It  is  more  reasonable  to  refer  tlie 
production  of  albuminuria  to  changes  in  the  capillary  walls  of  the  glomeruli 
than  to  desquamation   or  other  alteration  of  the  glomerular  epithelium. 


300  EXPERIMEXTAL  STUDY  OF 

Certainly  some  swelling  and  desquamation  of  this  epitlielium  are  extremely 
common,  even  in  cases  without  renal  sj-mptoms. 

But  while  I  am  disposed  to  attach  such  importance  to  alterations  of  the 
glomerular  capillaries,  we  are  not  justified  in  asserting,  as  has  heen  done, 
that  these  changes  constitute  the  primary  and  essential  lesion  of  all  cases 
of  Bright's  disease.  The  glomerular  lesions  are  coordinate  with  the  paren- 
chymatous, the  interstitial,  and  the  other  vascular  lesions  of  diffuse  nephritis. 

As  regards  nomenclature,  there  is  not  much  use  in  fighting  against  names 
which  have  gained  currency,  although  the  term  glomerulitis  seems  to  be  more 
suitable  than  glomerulo-nephritis,  and  equally  expressive.  It  is  customary 
to  include  all  of  the  changes  of  the  ^Malpighian  bodies  which  are  not  either 
atrophic  or  purely  degenerative,  under  tlie  name  glomerulo-nephritis ;  but  it 
is  to  be  borne  in  mind  tliat  this  term  is  used  to  designate  a  group  of  lesions 
belonging  to  diffuse  nephritis,  and  not  a  disease  by  itself.  I  would  suggest 
that  the  form  characterized  by  an  accumulation  of  cells  between  tiie  glomer- 
ulus and  Bowman's  capsule  be  designated  desquamative  glomerulitis,  and 
that  characterized  by  accumulation  of  cells,  or  other  changes  in  the  interior 
of  the  capillaries,  be  called  intra-capillary  glomerulitis,  and  this  without 
prejudging  tlie  question  as  to  the  propriety  of  considering  all  of  these  changes 
as  inflammatory. 

**  ******** 

DISCUSSION 

Dk.  Welch. — Experiments  liave  been  performed  by  Guarnieri  and  Ago- 
stinelli  whicli  bear  ujx)n  tlie  points  raised  by  Dr.  Jacobi.  In  a  fatal  case  of 
cantharidin  poisoning  in  a  human  being  these  observers  failed  to  find  marked 
lesions  of  the  kidney,  such  as  had  been  described  by  Cornil  in  his  experi- 
ments on  rabbits.  They  concluded  that  these  severe  lesions  occur  only  when 
the  cantharidin  is  administered  subcutaneously,  and  not  when  it  is  taken 
into  the  stomach.    This  conclusion  they  confirmed  by  experiments  on  rabbits. 

It  is  said  that  cantharidin  acts  upon  various  organs  of  the  body,  producing 
changes  especially  in  the  capillary  endothelivmi.  I  have  confined  my  atten- 
tion to  the  kidney,  my  purpose  being  not  so  much  to  study  the  action  of  can- 
tharidin as  such,  but  to  investigate  certain  lesions  of  the  ^lalpighian  bodies. 

As  to  the  permanency  of  the  alterations  of  the  glomeruli,  this  depends 
upon  their  character.  'J'he  accumulation  of  cells  in  the  capsular  space  has 
nothing  about  it  which  is  irremediable. 

Whether  or  not  we  arc  to  regard  this  or  some  other  change  of  the  glomeruli 
as  the  necessary  starting-point  of  acute  and  chronic  Bright's  disease  it  is 
impossil)le  to  say  j)ositively.  It  seems  to  me  that  our  j)resent  knowledge 
does  not  justify  us  in  assigning  to  any  one  particular  process  the  origin  of 
the  different  forms  of  nephritis.  It  is  sufficient  to  describe  the  various 
processes  occurring  in  Bright's  disease,  without  expressing  positive  opinions 
as  to  the  dependence  of  one  process  upon  another. 


GLOMERULO-NEPHEITIS  301 

I  do  not  wish  to  be  niisuiidorstood  in  regard  to  the  use  of  tlie  term  glo- 
merulo-nephritis.  I  do  not  understand  this  to  indicate  a  separate  disease  of 
the  kidney.  The  term  glomerulo-nephritis  or  glomerulitis  is  a  convenient 
one  to  designate  all  of  the  changes,  not  degenerative  or  purely  atropliic 
which  occur  in  the  Malpighian  bodies. 

I  tliink  that  too  much  importance  is  sometimes  attached  to  mere  desqua- 
mation of  the  capsular  and  of  the  glomerular  epithelium.  This  desquama- 
tion is  a  very  common  condition  even  when  there  is  not  much  disease  of  the 
kidney,  and  when  there  have  been  no  marked  renal  symptoms  during  life.  I 
question  the  propriety  of  attributing  all)uniinuria  to  changes  in  the  glomer- 
ular epithelium.  There  is  more  retuson  to  suppose  that  changes  in  the  walls 
of  the  glomerular  capillaries  are  the  essential  factor  in  the  production  of 
albuminuria.  The  capillaries  of  the  glomerules  differ  in  structure  from  the 
capillaries  in  other  parts  of  the  body,  and  these  differences  may  explain  the 
fact  that  normally  they  do  not  permit  the  transudation  of  an  albuminous 
lluid. 


THE  CARTWEIGHT  LECTURES 

ON  THE  GENERAL  PATHOLOGY  OF  FEVER' 

Lecture  I 

THE  NATURE  OF  FEVER 

There  is  no  subject  in  medicine  of  more  general  and  varied  interest  than 
fever.  The  practitioner  in  every  department  of  medicine,  the  pathologist 
and  the  physiologist  are  equally  interested  in  the  investigation  of  the  nature 
and  effects  of  fever.  Even  the  physicist  and  the  chemist,  who  are  not  directly 
concerned  with  medical  science,  have  lent  their  aid  to  the  study  of  animal 
heat  and  its  disorders.  The  history  of  opinion  regarding  fever  is  in  great 
part  the  history  of  medicine  itself,  for  no  feature  of  the  great  systems  of 
medicine  from  Hippocrates  and  Galen  to  the  present  century  so  character- 
izes these  systems  as  the  views  held  concerning  the  nature  of  fever.  In  con- 
sequence of  the  importance  of  the  subject  and  of  the  number  and  ability  of 
those  engaged  in  its  investigation,  it  might  be  supposed  that  no  chapter  in 
medical  science  would  be  better  understood  than  tliat  pertaining  to  fever. 
That  such  is  not  the  case  is  due  to  the  fact  which  is  becoming  more  and  more 
evident  that  the  reaction  of  the  animal  system  wliich  we  call  fever  is  depen- 
dent upon  the  most  fundamental  and  essential  properties  of  protoplasm  and 
of  nerve  energy.  In  proportion  as  our  knowledge  of  these  properties  in- 
creases and  becomes  more  accurate,  we  gain  a  clearer  insight  into  the  com- 
plicated processes  involved  in  the  production  of  fever. 

I  should  hardly  have  selected  for  this  course  of  lectures  a  subject  where 
so  many  problems  remain  unsolved  and  which  must  necessarily  be  presented 
in  so  fragmentary  a  form,  were  it  not  that  in  all  ages  the  opinions  lield  con- 
cerning the  nature  of  fever  have  controlled  measures  employed  in  its  treat- 
ment. In  proof  of  this,  one  need  not  go  back  to  the  time  when  fever  was  re- 
garded as  an  almost  conscious  struggle  of  an  anima  with  a  noxious  principle, 
in  v/liich  struggle  the  physician  was  to  interfere  as  little  as  possible,  or  to 
the  time  when  fever  was  supposed  to  result  from  morbid  humors  which  the 
physician  should  aim  to  eliminate  by  the  production  of  a  critical  discharge,  or 
to  tlie  period  when  the  treatment  hinged  u])on  the  belief  either  in  tlie  sthenic 

*  Delivered  before  the  Association  of  the  Alumni  of  the  College  of  Physicians  and 
Surgeons,  New  York,  March  29,  April  5  and  12,  1888. 
Med.  News,  Phila.,  1888,  LII,  365;  393;  539;  565. 

302 


GENERAL  PATHOLOGY  OF  FEVER  303 

or  the  asthenic  nature  of  fever.  In  our  own  time  the  treatment  of  fever  is 
intimately  connected  with  the  answers  variously  given  to  such  questions  as 
whether  fever  aids  in  the  elimination  or  destruction  of  infectious  agents 
concerned  in  its  production ;  whether  increased  waste  of  tis^^ue  is  a  constant 
condition  and  a  source  of  danger  in  fever ;  what  part  is  played  by  infection 
and  what  part  by  elevation  of  temperature  in  causing  the  grave  symptoms  of 
fever;  what  in  addition  to  lowering  of  temperature  are  the  effects  of  so- 
called  antipyretic  measures  of  treatment? 

I  need  hardly  say  that  the  subject  of  these  lectures  relates  to  fever  as  a 
condition  common  to  all  febrile  diseases.  Some  writers  understand  by  the 
term  fever  ut^ed  in  this  sense  merely  abnormal  elevation  of  temperature, 
others  elevation  of  temperature  and  the  symptoms  directly  caused  by  this, 
and  still  others  a  (•(ini])k'x  of  syni])t(nns  of  wliit-li  increased  temperature  is 
the  most  prominent  but  not  necessarily  the  cause  of  the  others.  In  con- 
sidering the  general  pathology  of  fever  it  is  convenient  to  adopt  the  last 
meaning,  although  it  would  doubtless  be  less  confusing  if  the  word  fever  were 
applied  only  to  abnormal  elevation  of  temperature. 

Increased  temperature  being  the  dominant  and  essential  system  of  fever, 
all  discussions  as  to  the  nature  of  fever  centre  around  the  question.  How 
is  the  febrile  rise  of  temperature  produced?  It  is  to  the  consideration  of 
this  question  that  I  first  invite  your  attention.  As  there  are  otner  aspects 
of  fever  which  I  wish  to  discuss,  it  will  be  necessary  to  present  the  matter 
belonging  to  this  division  of  the  subject  in  as  succinct  a  form  as  is  com- 
patible with  clearness.  T'welve  years  ago  Burdon- Sanderson '  brought  to- 
gether in  an  admirable  critical  review  the  results  of  investigations  upon  this 
subject  up  to  that  period.  Since  that  time  important  additions  have  been 
made  to  our  knowledge  of  the  mode  of  production  of  fever. 

In  the  wonderful  preservation  of  a  nearly  constant  temperature  which 
characterizes  in  health  the  warm-blooded  animals  three  factors  are  con- 
cerned, viz.,  the  production  of  heat  within  the  body,  the  loss  of  heat  from 
the  body,  and  the  regulating  mechanism  by  which  the  varying  heat  produc- 
tion and  heat  loss  are  so  balanced  tliat  the  internal  temperature  remains 
practically  constant.  It  is  theoretically  possible  that  the  rise  of  temperature 
in  fever  may  be  due  to  tlie  disturbance  of  any  one  or  more  of  these  factors. 
It  becomes  necessary,  therefore,  to  consider  the  behavior  of  heat  production, 
of  heat  loss,  and  of  the  regulating  mechanism  in  fever. 

We  will  begin  with  the  consideration  of  the  production  of  heat  in  fever. 
The  amount  of  heat  produced  by  the  body  is  estimated  by  two  methods,  one 
known  as  direct  calorimetry,  the  other  as  indirect  calorimetry.  In  the 
method  of  direct  calorimetry  the  animal  is  placed  in  a  closed  ventilated  box 

'  Burdon-Sanderson :   The  Practitioner,  1876. 


304  CAETWRIGHT  LECTURES 

surrounded  on  all  sides  by  a  compartment  containing  water  or  air,  and  the 
amount  of  heat  discharged  from  the  body  is  determined  by  the  quantity  of 
heat  imparted  to  the  surrounding  water  or  air.  If  the  temperature  of  the 
animal  remain  unchanged  during  the  period  of  observation,  the  heat  pro- 
duction is  equal  to  the  heat  loss ;  if  the  temperature  rise  or  fall,  the  amount 
of  heat  corresponding  to  this  change  of  temperature — an  amount  determined 
by  multiplying  the  weight  of  the  animal  by  its  specific  heat  and  by  the 
number  of  degrees  of  altered  temperature — is  added  to  or  sulitracted  from 
the  quantity  of  heat  imparted  to  the  calorimeter.  Time  will  not  permit  me 
to  enter  into  experimental  details  in  this  connection ;  it  must  suffice  to  say 
that  the  method  of  direct  calorimetry  necessitates  the  introduction  of  a  num- 
ber of  corrections  which  cannot  be  determined  with  absolute  accuracy,  so  that 
the  results  obtained  are  of  relative  rather  than  of  absolute  value. 

Hitherto  the  estimation  of  heat  production  in  fever  by  determining  the 
entire  amount  of  heat  liberated  from  the  body  has  been  made  only  upon 
animals  in  which  fever  has  been  artificially  produced.  The  most  elaborate 
researches  of  this  nature  are  those  of  Senator  *  and  of  Wood.*  Tiie  experi- 
ments of  Wood  are  of  the  greater  value  because  he  extended  his  observations 
over  longer  periods  of  time. 

In  four  of  the  seven  calorimetrical  experiments  of  Wood  on  difTerent 
fevered  dogs  comparison  can  be  made  of  the  amount  of  heat  produced  hourly 
in  fever  with  that  produced  by  the  same  animal  when  fed  and  when  in  a 
state  of  hunger.  During  the  period  of  fever  the  animal  was  also  in  a  con- 
dition of  hunger.  I  have  computed  from  Wood's  tables  that  the  average 
hourly  heat  production  during  seven  days  described  as  first  and  second  fever 
days,  is  a  little  over  23  per  cent  greater  than  that  of  the  healthy  animal  dur- 
ing a  state  of  hunger,  the  minimum  excess  being  1  per  cent  and  the  maxi- 
mum 55.5  per  cent'  If  a  comparison  be  made  of  different  periods  during 
the  existence  of  fever  there  are  found  to  be  even  greater  fluctuations  m  tlie 
amount  of  heat  production  than  these  figures  would  indicate,  this  amount 
being  sometimes  more  than  double  that  in  hunger  and  sometimes  consider- 
ably less  than  the  average  production  in  hunger.  Moreover,  these  experi- 
ments show  no  definite  relation  between  the  height  of  the  tenii)erature  and 
the  amount  of  heat  produced,  nor  is  it  possible  to  deduce  from  them  any 
relation  between  heat  production  and  the  different  stages  of  fever,  such  as 
the  more  recent  calorimetrical  experiments  of  Wood,  Reichert,  and  Hare  * 

»  Senator:    Untersuchungen  iiber  d.  Fiebcrhaftcn  Process,  Berlin,  1873. 

♦Wood:    Fever,  A  Study  In  Morbid  and  Normal  Physiology,  Philadelphia,  1880. 

*  In  making  this  computation  I  have  corrected  some  numerical  errors  in  Wood's 
tables;  these  errors  are  not  serious  and  do  not  affect  his  conclusions. 

*  Wood,  Reichert,  and  Hare:    Therapeutic  Gazette,  1886. 


GENERAL  PATHOLOGY  OF  FEVER         305 

appear  to  show  and  which  will  be  described  later.  An  important  outcome  of 
these  as  well  as  of  all  similar  calorimetrical  experiments  is  that,  although 
the  heat  production  of  an  animal  in  fever  is  greater  than  that  under  like 
conditions  of  nourishment,  it  is,  as  a  rule,  less  than  that  of  the  same  animal 
upon  a  full  diet. 

There  are  many  reasons  which  make  it  important  to  control  the  experi- 
mental results  obtained  from  animals  in  fever  by  corresponding  observa- 
tions of  human  beings.  The  agents  used  in  producing  experimental  fever 
have  been  generally  putrid  fluids  or  pus,  the  injection  of  which  causes  some- 
times diminution  instead  of  elevation  of  temperature.  When  fever  is  thus 
produced,  it  is  usually  of  short  duration  and  of  only  moderate  intensity, 
the  rise  of  temperature  being  rarely  more  than  four  degrees,  and  sometimes 
not  more  than  one  degree  Fahrenheit.  Moreover,  a  large  part  of  the  im- 
portant role  played  by  the  skin  in  the  regulation  of  the  bodily  temperature  in 
man  is  assumed  by  the  lungs  in  these  animals. 

Complete  calorimetrical  observations  of  human  beings  in  fever  encounter 
difficulties  which  have  not  yet  been  overcome.  The  imperfect  or  incomplete 
methods  employed  by  Liebermeister '  and  by  Leyden  *  in  determining  the 
heat  production  of  human  beings  in  fever  justify  the  inference  that  this 
production  is  increased,  and,  apparently,  as  a  rule,  to  a  greater  extent  than 
in  animals,  but  they  do  not  warrant  positive  conclusions  as  to  the  quantity 
of  heat  produced. 

We  turn  now  to  the  results  regarding  febrile  production  of  heat  obtained 
by  what  has  sometimes  been  called  indirect  calorimetry.  Inasmuch  as  the 
heat  energy  of  the  body  is  the  result  of  chemical  changes  of  its  proteids,  fats, 
and  carbohydrates,  it  is  evident  that  if  we  know  the  kind  and  the  amount 
and  the  heat  value  of  the  substances  consumed  in  a  given  time  within  the 
body,  we  can  compute  their  heat  production.*  These  chemical  changes,  so 
far  as  their  final  products  are  concerned,  are  processes  of  oxidation.  The 
heat  values  of  the  substances  consumed  in  the  body  were  determined  first  by 
Frankland  and  more  recently  with  accuracy  by  von  Rechenberg,  Danilewsky, 
and  Rubner.  The  investigations  of  Pettenkofer  and  Voit  have  shown  that 
in  hunger  almost  exclusively  fats  and  proteids  are  oxidized,  and  that  in  this 
condition  by  determining  the  amount  of  oxygen  absorbed  and  of  nitrogen 

'Liebermeister:    Handb.  d.  Path.  u.  Therap.  d.  Fiebers.    Leipzig,  1875. 

*  Leyden:    Deutsches  Arch.  f.  klin.  Med.,  Bd.  5. 

•  The  energy  resulting  from  these  chemical  changes  appears  partly  in  the  form 
of  heat  and  partly  in  mechanical  work.  As  practically  all  of  the  internal  mechan- 
ical work  is  transformed  within  the  body  into  heat  energy,  it  is  only  the  external 
mechanical  work  which  is  to  be  considered  in  estimating  the  actual  heat  produc- 
tion.   The  influence  of  this  factor  in  fever  will  be  spoken  of  later. 


306  CARTWRIGHT  LECTURES 

and  of  carbon  excreted,  we  can  estimate  the  quantity  of  fat  and  of  proteid 
substances  oxidized  during  the  period  of  observation. 

Physicians  of  past  centuries  regarded  increased  consumption  of  the  ma- 
terial of  the  body  in  fever  as  so  eWdent  that  it  needed  no  especial  demonstra- 
tion, and  after  Lavoisier  made  apparent  the  sources  of  animal  heat,  it  was 
accepted  almost  unquestioningly  until  the  last  quarter  of  a  century  that 
fever  is  essentially  a  process  of  increased  combustion  or  oxidation.  The  im- 
mense liistorical  importance  of  the  promulgation  in  1863  of  Traul)e's  theory, 
which  denied  the  dependence  of  fever  upon  increased  production  of  heat, 
is  that  this  theory  has  led  to  a  careful  inquiry  into  the  grounds  of  beliefs 
hitiierto  generally  accepted,  and  to  the  demonstration  of  the  unsatisfactory 
nature  of  the  evidence  hitherto  thought  to  be  conclusive. 

The  striking  loss  of  weight  of  most  fever  patients  is,  as  is  well  known,  a 
fact  of  great  clinical  importance.  Weber,  and  Finkler  have  demonstrated 
that  animals  in  fever  lose  weight  more  rapidly  than  healthy  animals  in 
hunger,  and  although  observations  on  human  beings  with  reference  to  this 
jxiint  are  not  concordant  in  their  results,  there  can  be  little  doubt  that  the 
tendency  of  fever  is  to  cause  a  greater  loss  of  weight  than  can  be  explained 
simply  by  insufficient  nutriment.  This  tendency,  however,  may  l)e  masked 
by  the  retention  of  water  within  the  body  as  the  investigations  of  Leyden 
and  others  have  shown.  While,  therefore,  the  studies  of  the  loss  of  weight 
in  fever  leave  no  doubt  that  there  is  increased  destruction  of  tissue  in  this 
condition,  we  cannot  consider  this  loss  as  an  accurate  measure  of  the  in- 
creased destruction,  nor,  without  further  knowledge,  as  an  indication  of 
increased  oxidation,  still  less  as  proof  of  excessive  production  of  heat. 

It  was  for  a  long  time  believed  that  the  excessive  excretion  of  urea  in  fever 
afforded  satisfactory  evidence  of  increased  oxidation  and  of  greater  produc- 
tion of  heat.  We  now  know,  especially  from  the  researches  of  A.  Frankel," 
that  this  is  so  far  from  being  true  that  we  could  explain  the  excessive  elimina- 
tion of  urea  better  upon  the  assumption  of  diminished  than  of  increased 
oxidation  of  tissue.  In  certain  pathological  conditions,  notably  phosphorus 
poisoning,  the  amount  of  urea  excreted  may  be  increased  more  tiian  tliree- 
fold,  notwithstanding,  or,  as  Frankel  believes,  in  consequence  of  diminished 
absorption  of  oxygen  and  elimination  of  carbonic  acid.  It  can,  moreover, 
be  comjmted  that  even  without  any  diminution  of  the  respiratory  gases  the 
discharge  of  urea  may  bo  increased  without  greater  production  of  heat. 
While,  therefore,  the  enormous  increjise  in  the  discharge  of  urea  in  fever 
sheds  valuable  light  upon  a  most  obscure  subject,  the  nature  of  febrile  me- 
tabolism, it  does  not,  regarded  by  itself,  afford  us  any  information  as  to  the 
production  of  heat. 

"  Frankel :    Vircliow's  Archiv.  Bd.  67. 


GENERAL  TATHOLOGY  Ob^  FEVER         307 

Failing  to  find  satisfactory  proof  of  increased  oxidation  in  tlie  loss  of 
weight  of  the  body,  or  the  excessive  excretion  of  urea  in  fever,  attention  was 
then  directed  to  the  elimination  of  carbonic  acid,  an  excretory  product  which 
bears  a  much  closer  relation  to  the  production  of  heat  than  does  urea.  Im- 
mense importance  has  been  justly  attached  to  the  determination  of  the 
amount  of  carbonic  acid  excreted  by  an  individual  in  fever.  No  point  in 
the  whole  battle-ground  of  fever  patliolog}'  has  been  more  hotly  contested 
than  whether  increased  production  of  cardonic  acid  is  an  essential  part  of 
the  febrile  process.  The  first  investigators  of  this  question,  Leyden,  Lieber- 
meister,  Senator,  contented  themselves  with- the  determination  of  the  amount 
of  carbonic  acid  ehminated  by  an  individual  in  fever  and  in  apyrexia.  There 
are  several  considerations  which  greatly  diminish  the  value  to  be  attached 
to  the  mere  estimation  of  carbonic  acid  excreted  without  simultaneous  de- 
termination of  the  amount  of  oxygen  absorbed.  As  has  been  urged  by  Sena- 
tor, and  with  especial  clearness  by  Pfliiger,  increased  discharge  of  carbonic 
acid  does  not  necessarily  imply  increased  production  of  the  same.  The  dis- 
charge of  carbonic  acid  varies,  independently  of  its  production,  with  the 
rhythm  and  depth  of  respiration,  and  with  the  temperature  and  the  alka- 
linity of  the  blood,  all  factors  which  are  altered  in  fever  in  such  a  manner 
as  to  favor  increased  liberation  of  carbonic  acid.  It  is  true  that  the  influence 
of  these  factors  would  cause  increased  discharge  of  carbonic  acid  out  of  pro- 
portion to  its  production  only  for  a  limited  period,  and  that  the  prolonged 
increase  in  the  amount  of  carbonic  acid  discharged  in  fever,  which  has  been 
found  by  several  observers,  can  hardly  be  interpreted  otherwise  than  in  favor 
of  increased  production.  There  is  another  point  which  detracts  still  further 
from  the  value  of  exclusive  determinations  of  the  quantity  of  carbonic  acid 
discharged,  and  this  is  that  it  makes  a  great  difference,  so  far  as  the  produc- 
tion of  heat  is  concerned,  whether  the  carbonic  acid  is  the  result  of  oxidation 
of  carbohydrates,  of  fats,  or  of  proteids,  a  difference  amounting,  according 
to  Rubner,"  to  29.5  per  cent;  or,  if  only  the  proteids  and  fats  be  considered, 
to  over  20  per  cent.  In  investigations  of  nutrition  it  is  now  known  to  be  of 
the  utmost  importance  to  determine  the  so-called  respiratory  quotient — 
that  is,  the  ratio  between  the  amount  of  carbonic  acid  discharged  and  that  of 
oxygen  absorbed.  This  quotient  varies  in  a  definite  way  with  the  kind  of 
material  oxidized  in  the  body,  and  an  accurate  knowledge  of  it  would  enable 
us  to  draw  conclusions  as  to  the  substances  consumed  in  fever. 

The  investigations  which  have  been  published  within  the  last  few  years 
upon  the  absorption  of  oxygen,  as  well  as  the  discharge  of  carbonic  acid  in 
fever,  are  to  be  ranked  as  most  valuable  contributions  to  our  knowledge  of 
the  subject.    The  first  determination  by  trustworthy  methods  of  the  amount 

"Rubner:    Zeitschrift  f.  Biologie,  Bd.  XXI. 


308  CARTWEIGHT  LECTURES 

of  oxygen  absorbed  and  of  carbonic  acid  excreted  in  fever  was  made  in 
Pfliiger's  laboratory  by  Colasanti  upon  a  guinea-pig,  and  was  published  in 
1877.  Since  that  time  two  careful  and  elaborate  researches  upon  this  sub- 
ject have  been  made,  the  one  by  Finkler,  and  the  other  by  Lilienfeld." 

These  experimenters  found  that  in  fever  tliere  is  increase  of  the  amount, 
both  of  oxygen  absorbed  and  of  carbonic  acid  excreted.  Making  comparison 
with  healthy  animals  under  the  same  conditions  of  nutrition,  Colasanti 
found  that  the  increase  in  the  absorption  of  oxygen  amounted  to  18  per  cent, 
and  in  the  excretion  of  carbonic  acid  to  24  per  cent;  Finkler,  whose  experi- 
ments were  made  also  upon  guinea-pigs,  found,  under  varying  conditions  of 
external  temperature,  the  average  febrile  increase  of  oxygen  to  be  13.8  per 
cent,  and  of  carbonic  acid  15.3  per  cent,  and  Lilienfeld,  who  experimented 
on  rabbits,  found  the  average  increase  of  oxygen  to  be  13.9  per  cent.  The 
statement  of  these  averages  gives  an  incomplet-e  conception  of  the  oxidation 
in  fever,  as  they  are  derived  from  all  stages  of  fever,  and  varying  elevations 
of  temperature.  No  constant  proportion  was  found  to  exist  between  the 
height  of  the  temperature  and  the  amount  of  oxidation.  On  the  other  hand, 
a  relation  was  observed  between  the  oxidation  and  the  stages  of  fever,  viz., 
the  initial  stage  with  rising  temperature,  the  acme  with  constant  high  tem- 
perature, and  the  defervescence  with  falling  temperature.  During  the  period 
of  rising  temperature  oxidation  was  increased,  and  in  this  stage  Finkler 
found  the  highest  percentages,  amounting  to  36.6  per  cent  in  the  increase 
of  oxygen,  and  37.6  of  carbonic  acid.  There  were,  however,  marked  fluctua- 
tions in  this  stage,  both  in  the  temperature  and  the  amount  of  oxidation. 
In  the  stage  of  constant  liigh  temperature  such  high  percentages  were  not 
noticed,  and  the  fluctuations  were  less  marked.  The  processes  of  oxidation, 
according  to  Lilienfeld,  are  increased,  on  tlie  average,  less  in  the  acme  than 
in  the  initial  stage  of  fever,"  During  defervescence  of  fever  the  increased 
oxidation  falls,  and  may  sink  below  the  normal.  Taking  a  broad  view  of 
these  stages,  we  may  say,  therefore,  that  the  periods  of  rising,  constant,  and 
falling  temperatures  in  fever,  correspond  to  periods  of  rising,  constant,  and 
falling  oxidation,  but  we  must  bear  in  mind  that  the  fluctuations  in  oxida- 
tion are  much  greater  than,  and  bear  no  constant  relation  to,  those  of  tem- 
perature; so  that,  in  each  period,  there  are  times  when  oxidation  .may  rise 
or  fall  most  decidedly  without  corresponding  changes  of  temperature. 

Inasmuch  as  these  experiments  have  shown  that  the  increased  excretion 
of  carbonic  acid  in  fever  is  accompanied  by  increased  absorption  of  oxygen, 

"Colasanti:  Pfliiger's  Archlv,  Bd.  XIV.  Finkler:  7&i4.,  Bd.  XXIX.  Lilienfeld: 
Ibid.,  Bd.  XXXII. 

"  In  the  period  of  rising  temperature  there  was  an  increase  of  oxygen  absorbed 
of  27  per  cent,  in  the  acme  of  14.9  per  cent. 


GENERAL  PATHOTjOGY  OF  FEVER         309 

and,  as  will  be  explained  presently,  that  the  respiratory  quotient,  if  it 
changes  at  all,  sinks,  it  is  evident  that  we  need  not  discard  experiments  in 
which  only  the  amount  of  carbonic  acid  excreted  has  been  estimated  by  good 
methods.  The  most  accurate  of  these  experiments  are  those  of  L^yden  and 
Frankel  upon  fevered  dogs."  They  found  that,  without  exception,  carbonic 
acid  is  excreted  in  larger  amount  in  fever  than  in  health  under  the  same 
nutritive  conditions,  the  excess  amounting  sometimes  to  70  per  cent,  and 
in  general  being  larger  than  in  the  experiments  which  have  been  previously 
considered.  The  earlier  and  meritorious  experiments  of  Senator  upon  this 
point  did  not  give  uniform  results,  and  he  felt  justified  in  concluding  that 
there  is  no  evidence  of  increased  production  of  carbonic  acid  in  fever.  Subse- 
quent experiments  with  far  more  accurate  methods  have  demonstrated  the 
incorrectness  of  Senator^s  conclusions.  It  may  be  well  to  call  to  mind  that 
Burdon-Sanderson's  deductions,  which  have  naturally  had  great  influence 
among  physicians  here  and  abroad,  were  based,  in  great  part,  upon  the  data 
derived  from  Senator's  experiments. 

Hitherto,  the  methods  employed  in  studying  the  respiratory  gases  of 
human  beings  in  fever  have  not  approached  in  accuracy  those  used  in  the 
experiments  described.  If  the  discordant  results  of  Wertheim,  which  were 
obtained  by  methods  manifestly  very  inaccurate,  be  discarded,  all  other  in- 
vestigators have  obsen'ed  augmented  discharge  of  carbonic  acid  in  fever  of 
human  beings.  Ley  den  found  an  excess  of  50  per  cent  in  the  febrile  dis- 
charge of  carbonic  acid;  and  Liebermeister,  whose  observations  were  made 
chiefly  on  cases  of  intermittent  fever,  found  an  excess  of  30  to  40  per  cent 
in  the  period  with  rising  temperature,  and  of  19  to  31  per  cent  in  the  acme 
of  the  fever.  During  the  deferversence  of  the  fever  the  excess  of  carbonic 
acid  discharged  diminished,  and  sometimes  wholly  disappeared.  In  one 
instance,  in  which  the  determination  was  made  during  the  rigor  of  intermit- 
tent fever,  the  carbonic  acid  excreted  was  two  and  a  half  times  the  normal 
amount;  an  excess  so  enormous  that  it  was  undoubtedly  due,  in  great  part, 
to  the  muscular  movements  which  attended  the  chill. 

Although  we  cannot  consider  these  figures  as  absolutely  accurate,  they 
indicate  clearly  that  in  human  beings,  as  well  as  in  animals,  fever  is  char- 
acterized by  increased  oxidation,  and  apparently  that,  as  a  rule,  in  man  the 
excess  of  oxidation  is  greater  than  in  the  experimental  fever  of  animals. 
This  was  to  be  expected,  as  it  is  difficult  to  produce  experimentally  in  animals 
anything  approaching  in  intensity  the  well-marked  fevers  of  human  beings. 

As  the  result  of  these  laborious  researches  we  may  consider  it  established 
that  increased  oxidation  is  a  part  of  the  fever  process.  It  has  been  claimed 
that  this  augmented  oxidation  is  simply  the  result  of  the  elevation  of  tem- 

^' Leyden  and  Frankel:    Virchow's  Archiv,  Bd.  76. 


310  CAETWRIGHT  LECTURES 

perature,  but  it  can  be  proven  that  this  is  not  true.  Pfliiger  has  demon- 
strated that  the  processes  of  oxidation  are  more  active  at  high  than  at  low 
temperatures  of  the  body,  and  he  lias  also  established  the  increment  of  oxi- 
dation which  corresponds  to  each  degree  of  rise  of  temperature.  By  means 
of  these  data  Finkler  has  computed  that  in  guinea-pigs  the  febrile  elevation 
of  temperature  of  1°  C.  could  cause  an  increase  of  the  absorption  of  oxygen 
of  only  3.3  per  cent.  Moreover,  Lilienfeld  found  decided  increase  in  the 
processes  of  oxidation  before  there  is  any  marked  elevation  of  temperature, 
and  all  the  experiments  have  rendered  it  quite  evident  that  there  is  no  such 
relation  in  fever  between  the  height  of  the  temperature  and  the  energy  of 
oxidation,  as  would  be  expected  if  the  augmented  oxidation  were  merely  the 
result  of  tlie  increased  temperature. 

I'hei'e  is  no  reasonable  doubt  that  the  more  energetic  oxidation  which  we 
find  to  be  an  essential  part  of  the  process  of  fever  indicates  increased  pro- 
duction of  heat.  Exactly  wliat  amount  of  heat  production  corresponds  to 
the  increased  oxidation  we  cannot  know  until  the  kind  and  the  quantity  of 
substances  oxidized  in  fever  have  been  determined.  It  is  to  be  regretted  tliat 
Tio  experiments  have  been  made  in  which  the  amount  of  nitrogen  excreted 
has  been  determined  at  the  same  time  with  the  estimation  of  the  oxygen 
absorbed,  and  of  the  carbonic  acid  discharged.  These  data  would  enable  us 
to  form  some  estimate,  although  not  an  accurate  one,  of  the  amount  of  heat 
production  corresponding  to  the  oxygen  absorbed,  unless  very  different  laws 
from  those  in  health  control  the  oxidation  processes  of  fever. 

Mention  has  already  been  made  of  the  importance  of  determining  in  fever 
the  respiratory  quotient,  or  the  ratio  between  the  carbonic  acid  discharged 
and  the  oxygen  consumed.  A  few  words  will  make  this  clear.  It  is  well 
known  tliat  under  ordinary  circumstances  in  health  not  all  of  the  oxygen 
consumed  reappears  in  the  carbonic  acid  discharged.  This  indicates  that 
a  part  of  the  oxygen  absorbed  is  used  in  other  oxidations  than  those  result- 
ing in  the  production  of  carbonic  acid.  According  to  the  extent  of  these 
other  oxidations,  therefore,  the  respiratory  quotient  must  vary.  It  is  prob- 
able that  these  oxidations,  of  which  carbonic  acid  is  not  a  product,  result  at 
least  in  part,  in  the  formation  of  water,  which  is,  therefore,  one  of  the  ex- 
cretory products  of  the  body,  as  has  been  urged  especially  by  Austin  FUnt. 
The  influence  of  various  circumstances  upon  the  respiratory  quotient  has 
been  studied,  but  what  especially  concerns  us  here  is  that  in  hunger  this 
quotient  sinks,  which  is  to  be  expected  from  the  fact  that  in  this  condition 
almost  exclusively  fats  and  proteids  are  oxidized.  We  evidently  possess  in 
tlie  determination  of  the  ratio  of  carbonic  acid  discharged  to  the  oxygen  con- 
sumed a  means  of  reaching  a  conclusion  as  to  a  cardinal  point  in  the  path- 
ology of  fever,  viz.,  whether  the  processes  of  oxidation   in  fever  conform 


GENERAL  PATHOLOGY  OF  FEVER         311 

to  the  laws  which  govern  them  in  liealth,  and  particularly  whether,  as  has 
been  often  asserted,  unusual  or  incomplete  products  of  oxidation  are  formed 
to  any  considerable  extent  in  fever.  Colasanti  and  Lilienfeld  found  that 
the  respirator^'  quotient  in  their  fevered  animals  did  not  vary  from  tliat  of 
healthy  animals  under  similar  nutritive  conditions.  Finkler  observed  that 
the  respiratory  quotient  fell  in  fever  somewhat  more  rapidly  than  in  hunger, 
and  this  he  explains  by  the  more  active  oxidation  in  fever.  All  three  ex- 
j)erimenters  reached  the  conclusion  that  the  substances  oxidized  are  the  same 
in  fever  as  in  health,  and  that  other  than  the  normal  products  of  combustion 
are  not  formed  in  fever  in  any  considerable  amount.  That  the  metabolism 
in  fever  does  dilfer  in  at  least  one  important  respect  from  that  in  hunger,  is 
evident  from  the  excessive  amount  of  urea  excreted  in  fever,  but  considerable 
variations  in  the  disintegration  of  albuminous  material  may  occur  witliout 
much  change  in  the  respiratory  quotient. 

The  only  determinations  of  the  febrile  consumption  of  oxygen  and  dis- 
charge of  carbonic  acid  in  man  are  those  of  Wertheim  and  of  Regnard.  Both 
investigators  found  a  decided  diminution  of  the  respiratory  quotient.  The 
method  employed  by  Wertheim  was  so  defective  that  no  confidence  can  be 
placed  in  his  results.  The  experiments  of  Regnard  "  are  presented  with  great 
neatness,  but  his  results  on  other  points  differ  so  much  from  those  obtained 
by  trustworthy  physiologists  and  by  better  methods,  that  we  cannot  accept 
his  conclusions  as  to  respiratory  quotient  in  fever  without  confirmation. 
Regnard  found  in  all  fevers  which  he  studied  a  most  marked  diminution  of 
the  respirator}'  quotient.  If  this  were  true  it  would  follow  that  in  fever  a 
much  larger  part  than  in  health  of  the  oxygen  consumed  is  employed  in 
other  oxidations  than  those  yielding  carbonic  acid.  This  would  confirm  the 
Avidely  accepted  belief  that  water  and  products  of  incomplete  oxidation  are 
formed  in  excessive  amount  in  fever. 

From  the  unfortunate  discrepancy  of  these  results  it  is  evident  that  the 
knowledge  which  we  now  possess  of  the  processes  of  oxidation  in  fever  is 
not  sufficient  to  enable  us  to  form  from  them  an  accurate  estimate  of  the 
heat  production.  In  hunger,  from  one-fourth  to  one-third  of  the  absorbed 
oxygen  is  available  for  combination  "with  hydrogen  to  form  water,  the  re- 
mainder uniting  with  carbon  to  fonn  carbonic  acid  (Regnault  and  Reiset). 
If  in  fever  the  same  ratio  exists,  then  the  excess  of  heat  production  would  be 
proportionate  to  the  excess  of  oxygen  absorbed,  assuming  that  the  substances 
oxidized  are  the  same  in  both  conditions;  if,  however,  as  Regnard's  experi- 
ments indicate,  a  larger  proportion  of  oxygen  is  available  in  fever  for  the 
oxidation  of  hydrogen,  then  tlie  increment  of  heat  production  would  be  still 

"Regnard:  Recherches  Exp.  sur  les  Variations  Pathologiques  des  Combustions 
Respiratoires.     Paris,  1878. 


312  CARTWRIGHT  LECTURES 

greater,  for  the  same  amount  of  oxygen  produces  more  heat  when  employed 
in  the  oxidation  of  hydrogen  than  in  that  of  carbon.  It  is  also  to  be  con- 
sidered that  the  same  quantities  of  hydrogen  and  of  carbon  in  their  oxida- 
tion yield  varying  amounts  of  heat  according  to  the  chemical  compounds  in 
which  they  are  contained,  and  we  cannot  say  positively  whether  the  com- 
pounds oxidized  are  the  same  in  fever  as  in  health  imder  like  conditions  of 
nutrition.  Upon  the  whole  the  weight  of  evidence  is  in  favor  of  the  view 
that  the  excess  of  heat  production  in  fever  is  approximately  proportionate 
to  the  increase  in  the  consumption  of  oxygen,  but  it  would  be  rash  to  assert 
this  positively.  It  is  evident  that  in  fever  ordinarily  a  much  smaller  amount 
than  in  health  of  the  energy  resulting  from  chemical  processes  is  transformed 
into  external  mechanical  work,  so  that  relatively  more  remains  in  the  form 
of  heat. 

In  connection  with  this  discussion  of  the  possibility  of  unusual  sources  of 
heat  in  fever  may  be  mentioned  an  hypothesis  which  has  been  advanced  with 
much  ingenuity  by  Dr.  Ord."  This  hypothesis  is  based  upon  the  assump- 
tion, which  is  probable  enough,  that  there  are  in  the  body  chemical  processes 
in  which  heat  energy  is  transformed  or  rendered  latent.  These  processes  are 
thought  to  be  chiefly  those  concerned  in  the  building  up  of  tissue.  It  is 
argued  that  inasmuch  as  the  construction  of  tissue  is  manifestly  in  abeyance 
in  fever,  the  amount  of  heat  in  the  body  may  be  increased  not  only  by  dis- 
integrative processes,  but  also  by  "  the  persistence  in  the  form  of  heat  of 
energy  which  should  have  taken  another  form."  That  these  building  up 
processes  influence  decidedly  the  amount  of  heat  produced  in  the  develop- 
ing ovum  has  been  demonstrated  by  d^ArsonvaFs  calorimetrical  determina- 
tion that  the  egg  during  incubation  absorbs  heat,  notwithstanding  the  con- 
sumption of  oxygen  and  the  excretion  of  carbonic  acid.  This  fact,  which 
might  have  been  predicted,  certainly  does  not  justify  us  in  refusing  to  attach 
any  calorimetrical  value  to  the  determination  of  the  respiratory  gases  and 
the  urinary  nitrogen.  From  the  little  we  know  of  these  constructive  proc- 
esses in  human  beings  we  should  infer  that  the  amount  of  energy  in  the  form 
of  heat  which  they  appro])riate  bears  only  a  very  small  ratio  to  the  total  heat 
energ}'  set  free  by  heat-producing  processes,  so  that  their  cessation  would  not 
bring  a  large  increment  to  the  heat  of  the  body.  Moreover,  these  construc- 
tive processes  arc  also  in  abeyance,  although  doubtless  to  a  less  extent,  in 
starvation,  with  which  experimental  fever  is  usually  contrasted  as  regards 
heat  production  and  heat  loss.  It  is  not  probable  that  any  extraordinary' 
ditference  in  the  behavior  of  the  processes  of  tissue-building  in  fever  and  in 
starvation  can  occur  without  affecting  the  respiratory  quotient.  For  tlie 
present,  therefore,  we  cannot  attach  any  great  importance,  so  far  as  the 

'•Ord:    British  Medical  Journal,  1885,  II. 


GENEEAL  PATHOLOGY  OF  FEVER         313 

increase  of  heat  energy  in  fever  is  concerned  to  the  inactivity  of  heat-ab- 
sorbing processes. 

We  have  gone  over  now  the  evidence  which,  in  my  judgment,  establishes 
the  fact  that  there  is  increased  production  of  heat  in  fever.  The  same  con- 
clusion is  reached  also  by  the  study  of  the  loss  of  heat  from  the  body  in 
fever.  That  fever  is  accompanied  by  increased  production  of  heat  and  by 
more  active  combustion,  has  been  in  all  ages  the  belief  of  the  majority  of 
physicians.  This  belief,  however,  has  been  rather  instinctive  than  based 
upon  actual  demonstration.  It  has  been  contested  by  investigators  of  great 
ability,  and  on  the  ground  of  scientific  observation.  For  these  reasons,  and 
on  account  of  the  importance  of  the  subject,  it  has  seemed  to  me  desirable  to 
pre.^ent  to  you  the  exact  evidence,  although  many  of  its  details,  I  fear,  may 
liave  wearied  you.  We  have  learned,  moreover,  certain  facts  concerning 
febrile  thermogenesis  which  the  mere  observation  of  fever  patients  does  not 
render  so  apparent.  We  have  found  that  there  is  no  definite  relation  between 
heat  production  and  the  height  of  the  temperature,  so  that  we  may  have 
excessive  thermogenesis  with  low  as  well  as  with  high  temperatures.  There 
appears  to  be,  however,  a  relation  between  the  stages  of  fever  and  heat  pro- 
duction, this  being  in  spite  of  remarkable  fluctuations  greatest  in  the  initial 
stage,  and  least  in  defervescence. 

Although  for  reasons  which  have  been  mentioned,  and  others  might  have 
been  adduced,  we  can  attach  hardly  an  approximative  value  to  figures  which 
purport  to  give  the  actual  heat  production  in  fever,  still,  unless  far  more 
serious  errors  than  seems  possible  in  here  in  the  methods  of  direct  and  of 
indirect  calorimetry,  we  can  draw  one  important  conclusion.  This  is  that 
while  an  individual  in  fever  produces  more  than  he  would  in  health  under 
similar  conditions  as  to  food  and  muscular  movements,  he  does  not  produce 
necessarily  in  fever  more  heat  than  he  would  in  health  on  a  full  diet.  And 
it  is  certain  that  he  usually  produces  far  less  heat  in  fever  than  he  often  does 
under  circumstances  which  normally  increase  heat  production,  such  as  a 
cool  environment  and  muscular  exercise.  That  one  in  health,  with  little  or 
no  change  of  temperature,  may  produce  twice  or  more  the  quantity  of  heat 
which  he  produces  in  fever,  makes  it  plain  that  it  is  impossible  to  explain 
febrile  rise  of  temperature  simply  on  the  basis  of  increased  thermogenesis, 
or  what  probably  comes  to  the  same  thing,  of  increased  oxidation.  That  in 
health  vastly  increased  heat  production  may  occur  with  comparatively  little 
change  of  temperature  is,  of  course,  due  to  the  fact  that  the  dissipation  of 
heat  is  proportionately  increased.  It  is  self-evident,  and,  so  far  as  I  know, 
has  never  been  disputed  tliat  in  fever  the  equilibrium  is  so  disturbed  that 
heat  loss  does  not  correspond  to  heat  production  as  it  should  in  health. 
This  disturbance  of  equilibrium  can  be  brought  about  in  various  ways,  and 


314  CARTWRIGHT  LECTURES 

it  is  only  by  the  determination  of  the  actual  heat  production  and  heat  loss 
in  fever  that  we  can  say  in  what  direction  the  balance  is  disturbed. 

We  have  found  that  th'e  production  of  heat  is  increased  in  fever  when  the 
comparison  is  made  with  like  conditions  of  nourishment  and  of  environment. 
It  is  obvious  that  the  total  loss  of  heat  cannot  equal  the  total  production  of 
heat  during  the  period  of  febrile  rise  of  temperature. 

As  is  well  known,  most  of  the  heat  of  the  body  is  liberated  from  the  skin 
and  from  the  lungs ;  from  the  former  by  radiation  and  conduction  and  by  the 
evaporation  of  moisture,  and  from  the  latter  l)y  evaporation  of  moisture 
and  warming  the  respired  air.  It  has  been  estimated  that  in  man  aljout 
eighty  per  cent  of  the  total  heat  dissipation  is  from  the  skin. 

The  method  of  direct  calorimetry,  already  described,  has  been  applied 
only  to  animals  for  the  determination  of  the  total  heat  loss  in  fever.  Here 
Wood's  experiments  are  the  best  which  we  possess.  Leyden  and  Liebermeis- 
ter  have  furnished  calorimetrical  data  which,  althougli  unsatisfactory  in 
many  respects,  indicate  the  general  direction  of  febrile  heat  loss  in  human 
beings.  All  of  these  experiments  show  that  more  heat  is  dissipated  in  fever 
than  under  like  conditions  in  health.  The  fluctuations  of  heat  loss  during 
a  febrile  paroxysm  are  so  great  that  the  statement  of  an  average  for  the 
entire  period  has  little  significance.  Such  an  average,  according  to  Wood's 
results  on  fevered  dogs,  would  fall  between  twenty  to  thirty  per  cent  excess 
of  lieat  loss  as  compared  with  the  loss  in  health  under  like  conditions  of  food. 
The  dissi])ation  of  lieat  in  fever,  however,  may  ])e  at  times  more  tlian  double 
the  normal  amount,  and  again  may  sink  below  the  norm.  We  have  not 
sufficiently  accurate  estimates  eitlier  of  the  total  amount  of  heat  produced 
or  of  that  dissipated  during  a  febrile  attack  to  enable  us  to  strike  a  balance 
between  the  two.  Some  })ersons  have  been  so  impressed  with  the  large 
amount  of  heat  lost  during  certain  periods  of  fever,  tliat  they  have  concluded 
that  there  must  ])e  far  greater  excess  of  heat  production  than  previous  in- 
vestigations have  sliown  to  be  probable.  Tlicy  suggest  tliat  there  are  sources 
of  febrile  heat  of  which  at  present  we  have  no  idea.  Such  conclusions  seem 
to  me  quite  unwarranted,  wlien  we  consider  the  ])eliavior  of  heat-loss,  not  for 
a  limited  time  but  tliroughout  the  dill'ercnt  stages  of  a  paroxysm  of  fever. 
We  have  already  seen  that  we  obtain  no  satisfactory  conception  of  febrile 
production  (tf  lieat  nidess  we  follow  it  during  the  stages  of  fever,  and  this 
is  no  less  true  of  heat  dissipation.  Tlie  observation  of  the  condition  of  the 
skin  as  regards  temperature  and  moisture  must  in  all  ages  have  afforded  an 
insight  into  the  general  behavior  of  beat  dissi])ation  during  the  different 
periods  of  fever.  It  does  not  require  any  instruments  of  precision  to  make 
plain  the  fact  that  a  cold,  dry  skin,  sucli  as  we  obser\c  dnriiig  a  febrile  chill, 
liberates  less  heat  than  normal,  or  that  a  hot,  moist  skin,  such  as  we  are 


GENERAL  PATHOLOGY  OF  FEVER         315 

likely  to  find  at  the  defenescenee,  loses  more  lieat  tlian  normal.  Not  quite 
so  evident  is  the  direction  of  heat  loss  duriii":  the  hot  stage  or  acme  of  a 
febrile  paroxysm  or  fastigium  of  a  continued  fever.  Here  the  skin  usually 
appears  hot  and  dry.  The  ordinary  impression  tliat  more  heat  than  normal 
is  dissipated  during  this  stage  is  supported  by  calorimetrical  experiments. 
There  can  be  no  doul)t  that  the  elevation  of  the  cutaneous  temperature  which 
we  observe  in  the  hot  stage  of  fever  causes  an  increase  in  the  amount  of  lieat 
lost  by  radiation  and  conduction.  Similar  elevations  of  cutaneous  tempera- 
ture in  health,  such  as  tliose  caused  by  muscular  exercise,  are  accompanied 
by  increased  moisture  of  the  surface.  Not  oiily  is  visible  perspiration  usually 
absent  during  the  hot  stage  of  fever,  Imt  the  invisible  perspiration  is,  as  a 
rule,  relatively  although  not  absolutely  diminished,  as  Leyden  has  shown. 
The  dryness  of  the  skin,  therefore,  is  a  factor  which  in  the  hot  stage  of  a 
fever  tends  to  lessen  heat  dissipation.  Clinical  observation,  however,  shows 
that  fevers  differ  markedly  from  each  other  as  regards  perspiration  during 
the  hot  stage,  the  skin  being  sometimes  bathed  in  perspiration  without  any 
depression  of  temperature.  It  would  undoubtedly  be  of  great  interest  to 
possess  trustworthy  data  as  to  the  exact  loss  of  water  from  the  surface  of 
the  body  in  different  fevers  and  at  different  stages  of  fever.  We  cannot  place 
much  reliance  upon  the  indications  afforded  by  Weyrich's  hygrometer,  which 
has  been  repeatedly  used  for  this  purpose,  ^lore  is  to  be  expected  from  the 
method  employed  by  Peiper "  in  studying  insensible  perspiration  under 
physiological  conditions. 

The  general  impressions  regarding  febrile  loss  of  heat  derived  from  clinical 
observations,  are  supported  by  calorimetrical  experiments.  The  dissipation 
of  heat  is  least  during  the  initial  stage  of  fever,  and  greatest  during  the 
period  of  defervescence.  During  the  hot  stage  or  fastigium  heat  dissipation 
exceeds  the  normal,  but  usually,  on  account  of  the  dryness  of  the  skin,  not 
so  much  as  one  might  infer  simply  from  the  impression  of  heat  received  by 
the  hand  when  placed  upon  the  skin. 

During  the  initial  period  the  loss  of  heat,  although  on  the  average  less 
than  in  the  following  stages,  is  usually  greater  than  normal.  If,  however, 
the  rise  of  temperature  be  rapid  the  heat  loss  falls  below  the  normal  amount. 
As  tliere  is  now  increased  production  of  heat,  there  is  evidently  a  glariiig 
disproportion  between  the  two  factors,  heat  production  and  heat  loss,  and 
under  these  circumstances  the  febrile  attack  is  likely  to  be  ushered  in  by  a 
chill.  During  the  febrile  chill  all  the  efforts  of  nature  combine  to  produce 
in  the  shortest  time  the  greatest  possible  elevation  of  temperature.  Not 
only  is  heat  loss  reduced  to  a  minimum,  but  heat  production  is  excited  to 
the  utmost. 

"Peiper:    Zeitschr.  f.  klin.  Med.,  Bd.  12. 


316  CARTWRIGHT  LECTURES 

During  the  period  of  defervescence,  on  the  other  hand,  the  relation  be- 
tween heat  loss  and  heat  production  is  reversed.  This  is,  of  course,  most 
apparent  when  the  fever  terminates  by  crisis  with  rapid  fall  of  temperature. 
Tiien  the  loss  of  heat  is  excessive,  being  sometimes  threefold  that  in  the 
normal  state,  and  the  production  is  relatively  and  often  absolutely  dimin- 
ished. 

It  is  of  importance  to  remember  that  there  are  continual  and  irregular 
fluctuations  in  the  dissipation  of  heat  during  the  different  stages  of  fever. 
These  fluctuations  bear  no  definite  relation  either  to  the  momentary  produc- 
tion of  heat,  or  to  the  height  of  the  internal  temperature.  We  deal  in 
ordinary  life  so  much  more  with  units  of  temperature  than  with  units  of 
heat  that  it  is  difficult  for  us  to  keep  constantly  in  mind  the  fact  that  no 
inference  can  be  drawn  as  to  the  height  of  the  internal  temperature  from 
the  knowledge  of  the  momentary^  heat  production  and  heat  loss.  If  the  heat 
loss  fall  behind  heat  production  the  temperature  of  the  body  rises,  and  it  can 
remain  at  this  elevated  point  with  either  diminished  or  increased  heat  pro- 
duction so  long  as  the  heat  loss  equals  heat  production. 

No  correct  conception  of  the  condition  of  the  heat-regulating  mechanism 
in  fever  can  be  obtained  without  taking  into  consideration  these  irregular 
variations  in  the  discharge  of  heat,  and  it  is  a  merit  of  Senator  and  his 
pupils  to  have  emphasized  particularly  this  point.  These  variations  are 
made  apparent  not  only  by  calorimetric  measurements  and  direct  observa- 
tion, but  also  by  the  studies  whicli  have  Ix-'en  made  of  the  cutaneous  tem- 
perature in  comparison  with  the  internal  temperature  in  fever.  Hankel's 
law  that  the  difference  between  the  temperature  in  the  axilla  and  that  of  the 
surface  of  the  body  in  the  febrile  condition  is  less  than  in  the  normal  con- 
dition manifestly  does  not  hold  for  tlie  chill,  in  which  it  has  been  proven 
that  the  superficial  temperature  falls  while  the  internal  temperature  rises. 
Jacobson,  Wegscheider,  Schiilein,"  find  that  there  constantly  occur  in  the 
course  of  most  fevers  changes  of  the  superficial  temperature,  which  stand  in 
no  relation  whatever  to  alterations  of  the  internal  temperature.  Schiilein 
thinks  that  he  has  discovered  some  facts  in  this  regard  whicii  are  available  in 
diagnosis.  However  this  may  be,  these  observations  indicate  that  contrac- 
tion and  dilatation  of  the  cutaneous  vessels  are  constantly  occurring,  and 
without  any  regularity,  in  fever.  These  irregular  variations  in  the  calibre 
of  the  bloodvessels  are  also  apparent  to  the  eye  in  the  vessels  of  the  rabbit's 
ear  during  fever.  When  it  is  considered,  furthennore,  that  these  irregulari- 
ties of  cutaneous  circulation  vary  decidedly  in  different  situations,  no  further 
proof  is  needed  that  the  mechanism  which  regulates  the  discharge  of  heat 
from  the  surface  of  the  body  is  profoundly  disturbed  in  fever. 

"Jacobson:  Virchow's  Archiv,  Bd.  65.  Schiilein:  7&td..  Bd.  66.  Wegscheider: 
Ibid.,  Bd.  69. 


GENERAL  PATHOLOGY  OF  FEVER         317 

These  alterations  in  cutaneous  circulation  are  such  striking  phenomena 
that  it  is  perhaps  not  surprisinor  that  two  great  medical  authorities  should 
have  based  upon  them  exclusively  theories  of  fever,  Traube  assuming  excita- 
tion and  Marey  paralysis  of  vaso-motor  nerv^es  as  the  primal  element  in  fever. 
We  need  not  discuss  these  theories,  now  generally  abandoned  in  their  ex- 
clusive form.  From  what  has  been  said  concerning  the  loss  of  heat  in  fever, 
it  is  evident  that  we  cannot  explain  febrile  rise  of  temperature  solely  by  the 
behavior  of  heat  dissipation  any  more  than  we  can  explain  it  solely  on  the 
basis  of  increased  heat  production.  In  rejecting  Traube's  theory  that  fever 
is  the  result  solely  of  retention  of  heat  we  must  still  recognize  the  fact  that 
decrease  in  the  dissipation  of  lieat,  at  times  absolute,  at  other  periods  relative, 
is  a  factor  of  the  utmost  importance  in  the  febrile  process. 

From  whatever  point  of  view  we  consider  the  question  we  cannot  avoid 
the  conclusion  that  it  is  tlie  meclianism  which  controls  the  relation  of  heat 
production  to  heat  loss,  whicli  is  disturbed  in  fever. 

Heat  production  is  increased  in  fever,  but  if  the  regulating  mechanism 
were  normal,  tlien  the  discharge  of  heat  would  be  proportionately  increased 
and  the  temperature  not  be  materially  affected.  Nor  would  the  force  of  this 
argument  be  changed  if  febrile  thermogenesis  were  twice  as  energetic  as  wc 
suppose  it  to  be. 

Tlie  loss  of  heat  is  increased  in  fever,  so  that  on  this  ground  alone  we 
sliould  be  obliged  to  assume  increased  heat  production.  But,  even  if  it  were 
proven  that  heat  dissipation  is  diminished,  as  has  been  recently  claimed 
again  by  Rosenthal,"  and  that  fever  is  the  result  of  heat  retention  alone,  it 
would  still  be  necessary  to  admit  that  the  regulating  mechanism  is  at  fault, 
for  Pfliiger  has  demonstrated  that  when  this  is  normal,  changes  in  the  tem- 
perature of  the  skin  are  attended  by  such  changes  in  heat  production  that 
the  internal  temperature  remains  within  wide  limits  unaltered. 

I  repeat  tlien  that  the  conclusion  is  forced  upon  us  that  the  fever-produc- 
ing agents  must  act  either  directly  or  indirectly  upon  the  mechanism  regu- 
lating the  harmonious  relation  of  licat  loss  to  heat  production. 

That  the  heat-regulating  mechanism,  although  profoundly  disturbed,  is 
not  entirely  paralyzed  in  fever,  is  proven  by  the  eff'ect  of  heat  and  cold  upon 
fevered  individuals.  Although  Colasanti  believed  that  his  fevered  guinea- 
pig  had  lost  all  power  of  heat  regulation  under  varying  external  tempera- 
tures, a  similar  conclusion  has  not  been  reached  by  others  who  have  investi- 
gated this  question. 

We  can  best  describe  the  condition  of  heat  regulation  in  fever  as  unstable 
or  ataxic.  External  cold  stimulates  to  some  extent  the  heat  production  of 
an  individual  in  fever,  but  by  no  means  as  much  as  it  does  in  health.     A 

"Rosenthal:    Deutsche  nied.  Wochenschrift,  1888. 


318  CAETWRIGHT  LECTURES 

person  in  fever  is  not  able  to  maintain  liis  bodily  temperature  under  the 
influence  of  lieat  and  cold  to  the  same  degree  that  he  can  under  normal  con- 
ditions. Liebermeister,  as  is  well  known,  held  that  heat  regulation  in  fever 
is  simply  adjusted  for  a  higlier  point,  although  he  admits  not  perfectly 
adjusted.  Experience  shows  that  this  so-called  adjustment  is  so  unstable 
that  it  does  not  seem  proper  to  compare  it  with  that  to  normal  temperatures 
in  health,  so  that  it  is  not  clear  what  deep  meaning  lies  in  Liebermeister's 
idea. 

We  cannot  imagine  the  heat-regulating  mechanism  to  be  other  than  a 
nervous  one. 

Some  years  ago  this  was  about  as  far  as  tlie  theory  of  the  mechanism  of 
fever  could  be  carried.  All  paths  led  to  tliis  mysterious  nervous  apparatus, 
and  beyond  this  nearly  all  was  speculation.  We  stood,  as  has  been  said, 
before  imposing  processes  veiled  in  the  deepest  obscurity.  Since  then  the 
veil  has  been  lifted  here  and.  there  and  we  have  caught  glimpses  of  the 
nature  of  these  processes.  I  refer  particularly  to  the  results  of  researches 
which  have  brought  to  light  a  more  immediate  and  direct  dependence  upon 
nerve  energy,  than  had  been  supposed,  of  chemical  processes  concerned  in  the 
disintegration  and  construction  of  tissue,  and  therefore,  in  the  production 
of  heat. 

With  one  side  of  the  nervous  mechanism  concerned  in  temperature  regu- 
lation, the  classical  investigations  of  Claude  Bernard  have  made  us  tolerably 
familiar.  This  is  the  vaso-motor  nervous  apparatus  presiding  over  tlie 
circulation  of  blood  in  the  superficial  parts  of  the  body,  and  thereby  con- 
trolling in  great  measure  the  discharge  of  heat.  That  the  important  part 
taken  by  the  perspiration  in  the  dissipation  of  heat  is  likewise  under  nervous 
influence,  has  been  demonstrated  by  Luchsinger.  The  facts  concerning  thi^ 
side  of  the  regulation  of  heat  are  too  well  known  to  require  elucidation  on 
this  occasion. 

Heat  regulation,  however,  is  effected  not  only  by  variations  in  tlie  elimina- 
tion of  heat,  but  also  by  changes  in  the  production  of  heat.  Familiar  as  the 
fact  is,  it  can  never  cease  to  arouse  our  admiration  tliat  the  temperature  of 
the  body  remains  the  same  in  cold  and  in  warm  atniosplieres.  Man  has  be- 
come vso  dependent  upon  clothing  that  in  the  naked  condition  his  capacity 
of  preserving  his  normal  temperature  in  a  cohl  environment  is  much  less 
tiian  tliat  of  most  animals.  Pfliiger  has  demonstrated  that  the  heat  regula- 
tion under  varying  external  temperatures  is  accomplished  by  changes  both 
in  heat  production  and  in  heat  loss,  so  that  in  a  cold  atnu)s])here  more  heat 
is  produced  and  in  a  warm  atni()S])here  less  heat,  provided  the  external  tem- 
perature is  not  so  high  or  so  low  as  to  make  it  physically  inipossihio  to  pre- 
serve the  body  temperature.     It  is  evident  that  this  is  the  most  rational  and 


GENERAL  PATHOLOGY  OF  FEVER         319 

economical  method  of  retaining  the  internal  temperature  of  the  body.  To 
regulate  the  body  temperature  simply  by  variations  in  the  discharge  of  heat, 
as  was  formerly  supposed  to  be  the  method,  would  be,  as  has  been  said,  like 
regulating  the  temperature  of  our  rooms  summer  and  winter  by  opening  and 
shutting  the  windows  without  controlling  the  source  of  heat. 

A  heat-producing  or  thermogenic  apparatus,  therefore,  is  no  less  a  part 
of  tlie  heat-regulating  mechanism  than  is  the  heat-discharging  or  thermo- 
lytie  apparatus,  to  use  the  terms  employed  by  Foster.  As  the  thermogenic 
apparatus  is  less  generally  understood  it  is  not  permissible  to  dismiss  its 
physiology  in  this  connection  so  briefly  as  I  have  the  thermolytic,  although 
our  knowledge  of  the  former  is  very  imperfect. 

I  can  assume  that  the  convincing  reasons  are  known  to  you  which  have 
led  physiologists  to  conclude  that  most  of  the  animal  heat  is  produced  in 
the  muscles  and  the  glands,  and  that  the  muscles  have  the  larger  share  in  this 
function.  It  is  also  well  known  that  stimulation  of  secretory  and  motor 
nerves  causes  not  only  visible  physical  alterations  in  the  glands  and  muscles, 
but  also  production  of  heat.  This  sort  of  dependence  of  heat  production 
upon  innervation  has  been  long  admitted.  It  may,  however,  not  be  so  gener- 
ally known  that  there  are  reasons  to  believe  that  nervous  impulses  control 
chemical  changes  which  result  in  the  production  of  heat  independently  of 
visible  pliysical  alterations  of  the  tissues;  in  other  words,  that  heat  produc- 
tion or  thermogenesis  is  at  least  in  considerable  part  under  the  immediate 
and  direct  control  of  the  nervous  system.  The  idea  is  not  a  new  one,  and 
was  advocated  especially  by  Claude  Bernard.  Recent  discoveries,  however, 
have  given  it  unexpected  support. 

This  subject  of  the  relation  of  innervation  to  thermogenesis  is  most  perti- 
nent to  the  patholog}'  of  fever,  but  it  is  essentially  a  physiological  one,  and 
as  I  wish  to  confine  to  a  single  lecture  what  I  have  to  say  concerning  the 
theory  of  fever,  it  is  impossible  for  me  to  do  more  than  summarize  the  most 
essential  points  belonging  here.  This  I  can  do  the  more  readily  as  Dr. 
MacAlister,^  in  his  admirable  Goulstonian  Lectures  on  the  "  Nature  of 
Fever,"  which  were  delivered  last  year,  has  clearly  and  forcibly  presented 
the  main  facts. 

The  larger  part  of  these  facts  relates  to  the  chemical  changes  and  heat 
production  of  muscles  under  varying  conditions. 

That  a  large  part  of  the  chemical  clianges  in  a  muscle  in  the  condition 
which  we  call  repose  is  under  the  influence  of  the  nervous  system,  is  made 
apparent  by  the  great  diminution  in  its  consumption  of  oxygen  and  forma- 
tion of  carbonic  acid,  which  follows  the  separation  of  the  muscle  from  all 
connection  with  the  central  nervous  system.    This  is  conclusively  shown  by 

=''MacAlister:    The  Lancet.  1887.  I. 


320  CARTWRIGHT  LECTURES 

the  experiments  of  Bernard,  Pfliiger,  von  Frey,  and  others.  It  is,  of  course, 
possible,  and  it  has  generally  been  supposed  that  under  these  circumstances 
it  is  simply  the  withdrawal  of  motor  impulses  which  lowers  the  heat-produc- 
ing energy  of  the  muscle. 

Far  more  suggestive  as  regards  the  point  under  consideration  are  the  re- 
sults of  investigation  which  have  been  carried  on  in  Ludwig's  laboratory  by 
Meade  Smith,  ^NlacAlister,  and  Lukjanow.  These  experimenters  have  shown 
that  heat  production  and  contraction  are  in  a  measure  independent  proper- 
ties of  the  muscle.  By  various  influences  the  thermogenic  property  may  be 
60  impaired  that  a  stimulus  causes  contraction  with  scarcely  any  develop- 
ment of  heat.  The  laws  governing  the  restoration  and  the  fatigue  of  the 
tliermogenic  function  differ  from  those  controlling  the  mechanical  function. 
These  researches,  upon  which  I  here  only  touch,  have  made  it  extremely 
probable  that  there  are  in  the  muscle  chemical  processes  resulting  mainly 
in  the  production  of  heat  and  chemical  processes  causing  mainly  contraction, 
and  that  these  processes,  although  coordinate,  are  not  identical.  A  new 
light  is  shed  upon  the  meaning  of  the  term  chemical  tonus  of  muscle,  which 
has  for  some  time  been  used  by  some  physiologists.  Great  caution  is  prop- 
erly exercised  by  Ludwig  and  his  pupils  in  the  interpretation  of  these  inter- 
esting results.  They  do  not  infer  from  them,  necessarily,  the  existence  of 
so-called  thermic  of  calorific  nerves.  They  suggest  that  it  is  possible  to 
explain  the  phenomena  upon  the  supposition  that  there  are  in  the  muscle 
two  kinds  of  material,  thermogenic  and  contractile,  and  the  nervous  impulses 
acting  upon  these  may  pass  through  the  same  set  of  nerves. 

Proof  of  the  existence  in  connection  with  muscles  of  thermic  in  distinc- 
tion from  motor  nerves,  would  be  afforded  if  we  could  succeed,  after  paralysis 
of  the  motor  nerves,  in  exciting  by  nerve  stimulation  the  tliermogenic  func- 
tion of  tlie  muscle.  We  possess,  in  curare,  a  drug  which  paralyzes  the  termi- 
nations of  the  motor  nerves.  jMeade  Smitli  attempted  by  its  aid  to  deter- 
mine whether  possible  thermic  nerves  may  be  differentiated  from  motor, 
but  he  reached  no  positive  conclusion  on  this  point.  There  are,  however, 
on  record  some  observations  which  suggest  the  possibility  that  in  moderate 
doses  curare  may  leave  intact  thermic  nerves  after  the  suspension  of  the 
function  of  motor  nerves.  When  an  animal  is  profoundly  under  the  influ- 
ence of  curare  tlie  internal  temperature  falls,  and  the  processes  of  oxidation 
are  greatly  reduced.  The  animal  is  no  longer  able  to  resist  the  changes  of 
external  temperature,  its  ovra  temperature  rising  and  falling  like  that  of  a 
cold-blooded  animal  when  exposed  to  heat  or  cold.  This  effect  of  curare 
poisoning  is  another  proof  of  the  dependence  of  heat  production  upon  nervous 
influences.  Claude  Bernard  in  his  early  researches  on  the  action  of  curare 
noted  elevation  of  temperature  soon  after  its  administration.     Voison  and 


GENERAL  PATHOLOGY  OF  FEVEE         321 

Liouville  "  observed  after  siilx-utaneous  injections  of  curare  in  man  rigors, 
perspiration,  headache,  and  elevation  of  temperature  to  104.7°  F.  They 
attribute  to  curare  the  power  of  producing  all  of  the  essential  phenomena  of 
fever.  Fleischer  "  noticed  in  dogs  and  in  rabbits  rise  of  temperature  after 
curare  injections,  and  tbe  same  was  observed  in  a  rabbit  in  one  case  by 
Hogyes.^  Recently  Mosso"  claims  that  an  animal  may  be  placed  so  far  under 
the  influence  of  curare  as  to  paralyze  completely  the  voluntary  muscles,  and 
the  internal  temperature  either  remain  normal  or  rise.  He  infers  that  these 
moderate  doses  of  curare,  although  sufficient  to  paralyze  the  motor  nerves, 
must  have  left  intact  the  thermic  nerves.  That  rise  of  internal  temperature 
is  not  due  to  retention  of  heat,  he  thinks  is  evident  from  the  normal  or  ele- 
vated temperature  of  the  skin.  Mosso  is  strengthened  still  further  in  his 
conclusion  as  to  the  existence  of  thermic  nerves,  by  finding  that  after  com- 
plete paralysis  of  the  motor  nerves  by  curare  injections  of  strychnine  cause 
an  elevation  of  rectal  temperature,  which  may  amount  to  three  degrees  centi- 
grade. Under  these  circumstances  strychnine  produces  no  spasms  or  other 
visible  mechanical  effect  upon  the  muscles.  Mosso  brings  forward  a  num- 
ber of  other  experiments  (decidedly  open  to  criticism)  intended  to  demon- 
strate the  existence  of  nerves  directly  controlling  heat  production,  but  tliose 
which  I  have  mentioned  are  by  far  the  most  striking.  It  seems  to  me  that 
the  natural  interpretation  of  these  experiments  is  in  favor  of  the  view  that 
there  are  nerves  controlling  heat  production  in  the  muscle  distinct  from 
motor  nerves.  Far  more  conclusive  as  to  this  point  than  thermometric  ob- 
servations would  be  calorimetric  experiments  determining  the  heat  produc- 
tion of  animals  under  varying  doses  of  curare. 

This  whole  line  of  experimentation  directed  toward  the  differentiation  of 
the  mechanical  and  the  chemical  functions  of  muscle  is  certainly  most  sug- 
gestive, but  so  long  as  the  interpretation  of  the  results  is  not  perfectly  clear, 
we  should  be  very  guarded  in  drawing  far-reaching  conclusions.  I  cannot 
refrain,  however,  from  pointing  out  that,  as  mentioned  by  MacAlister,  all 
of  these  thermogenic  phenomena  may  be  found  eventually  to  depend  upon 
nerves  whose  chief  function,  on  the  one  hand,  is  the  disintegration,  the 
metabolism  of  tissue,  and,  on  the  other  hand,  the  restoration,  the  auabolism 
of  tissue.  From  the  study  of  the  electrical  changes  which  stimulation  of  the 
pnemnogastric  nerve  produces  in  the  heart  muscle,  Gaskell  concludes  that 
this  nerve  puts  the  heart  in  a  condition  of  relative  rest  during  which  the 
energy  of  tbe  muscle  is  increased.     During  this  period  there  is  reason  to 

^  Voison  and  Liouville:    Virchow  u.  Hirsch's  Jahresbericht,  1866,  I,  p.  330. 

"  Fleischer:    Pfliiger's  Archiv,  Bd.  II,  p.  441. 

''Hogyes:    Arch.  f.  exp.  Path.  u.  Pharm.,  Bd.  XIV,  p.  136. 

'•*  Mosso:    Virchow's  Archiv,  Bd.  106. 


3^2  CARTWRIGHT  LECTURES 

believe  that  the  material  of  the  muscle,  which,  when  disintegrated,  gives  rise 
to  heat  and  mechanical  work,  is  in  the  process  of  restoration.  Hence  Gaskell 
sj)eaks  of  the  pneumogastric  or  inhibitory  nerve  of  the  heart  as  anabolic — 
that  is,  it  directs  the  restorative,  formative,  anabolic  processes  in  the  muscle. 
On  the  other  hand,  the  accelerator  nen'e  of  the  heart  induces  the  opposite 
electrical  changes  in  the  heart  muscle.  Gaskell  describes  this  nerve  as  katab- 
olic — that  is,  its  stimulation  causes  disintegration  of  the  muscle  materials, 
and  liberates  energy  in  the  form  of  heat  and  of  mechanical  work.  If  it  be 
found  that  similar  inhibitory  and  accelerator  nerves  preside  over  the  chemical 
changes  in  the  voluntary  muscles  and  other  tissues  of  the  body,  then  Gas- 
kelFs  induction  as  to  the  existence  of  anabolic  and  katabolic  nerves  must  be 
regarded  as  one  of  the  most  important  and  profound  in  modem  physiology, 
Thermo-excitory  nerves  we  should  then  rank  as  katabolic,  thermo-inhil)itory 
as  anabolic. 

These  investigations  tending  to  demonstrate  the  independent  existence 
of  thermogenic  properties  in  the  muscles  and  possibly  of  nerves  directly  con- 
trolling thermogenesis,  have  prepared  us  for  the  consideration  of  the  relation 
of  the  central  nervous  system  to  the  heat-producing  properties  of  the  body. 
Here  you  will  willingly  permit  me  to  confine  my  remarks  to  the  more  essen- 
tial and  best  established  facts,  without  entering  into  a  full  discussion  of  one 
of  the  most  perplexing  subjects  in  the  physiology  of  the  nervous  system. 

The  clinical  basis  of  the  doctrine  that  lesions  of  the  central  nervous  system 
influence  directly  the  temperature  of  the  body  was  laid  by  Sir  Benjamin 
Brodie,  who  reported  the  well-known  case  of  fracture  of  the  cervical  verte- 
brae and  injury  of  the  spinal  cord  followed  within  a  few  hours  by  a  rise  of 
temperature  to  111°  F.  measured  between  the  scrotum  and  the  thigh.  Since 
then  many  similar  instances  have  been  reported.  It  is  well  to  remember,  in 
framing  theories  on  tlie  basis  of  these  cases,  that  there  are  also  on  record  not 
a  few  instances  in  which  apparently  similar  injuries  of  the  same  parts  of  the 
spinal  cord  have  been  followed  by  equally  striking  fall  of  temperature. 

The  experimental  basis  for  the  acceptance  of  an  influence  of  the  nervous 
system  on  temperature  was  laid  by  Bernard,  in  his  celebrated  experiments  on 
the  effects  of  division  of  the  sympathetic  nerve  in  the  neck.  Bernard  inter- 
preted the  increased  temperature  of  the  ear  following  this  operation  as 
referable  not  only  to  the  larger  amount  of  blood  in  the  part,  but  also  to 
increased  tissue  metamorphosis  and  consequent  heightened  heat  production. 
The  latter  part  of  this  interpretation  is  not  generally  accepted.  It  may  be 
said  here  that  the  common  idea  that  an  organ  or  tissue  simply  because  it 
receives  a  larger  supply  of  blood  indulges  in  more  active  metabolism  is 
opposed  by  the  investigations  of  I^fliiger,  who  finds  that  the  amount  of 
oxygen  taken  up  by  the  cells  depends  in  a  far  higher  degree  upon  the  state 


GENERAL  PATHOLOGY  OF  FEVER         323 

of  their  innervation  at  the  time  than  it  does  upon  the  supply  of  oxygen.  The 
demand  of  the  tissues  for  oxygen  is  not  increased  simply  hecause  the  supply 
is  greater.  The  arguments  upon  which  Pfliiger  bases  this  line  of  reasoning, 
although  not  \\athout  opposition,  would  dispose  of  the  idea  that  when  any 
considerable  increase  of  heat  production  in  the  muscles  occurs  this  can  be 
explained  simply  by  vasomotor  changes.  I  mention  this  here,  because  the 
opinion  has  been  advanced  that  a  large  part  of  the  increased  production  of 
heat  in  fever  and  after  certain  injuries  to  the  nervous  system  is  referable 
simply  to  vasomotor  changes  in  the  muscles. 

In  1866  Tscheschichin'"  published  experiments  which  he  interpreted  as 
indicating  the  existence  in  the  brain  of  centers  which,  when  irritated,  moder- 
ate the  production  of  heat,  and  which  he  called  heat-moderating  or  heat- 
inhibitory  centres,  and  in  the  spinal  cord  of  centres  which  when  stimulated 
excite  the  production  of  heat,  heat-excitive  centres.  These  conclusions  were 
not  justified  by  the  experiments,  but  they  have  been  widely  accepted. 

I  may  here  say  that,  in  this  connection,  I  use  the  term  heat  centre  as  a 
convenient  and  generally  adopted  one.  There  is  a  proper  reaction  against 
the  prevailing  misuse  of  the  word  centre  for  all  sorts  of  little  understood 
localization  of  nervous  functions.  It  would  undoubtedly  be  more  accurate 
to  use  some  such  expression  as  thermically  active  region  instead  of  heat 
centre. 

It  is  not  easy  to  reconcile  the  clinical  fact  that  in  human  beings  lesions 
of  the  spinal  cord  may  be  followed  at  once,  or  in  a  very  short  time,  by 
extraordinary  elevations  of  temperature  with  the  results  of  experiments  on 
animals.  That  the  rise  of  temperature  in  human  beings  is  not  due  to  inflam- 
matory fever  is  apparent  from  the  rapidity  with  which  it  follows  the  injury. 
It  cannot  be  explained  by  vasomotor  lesions,  for  the  paralysis  of  the  vaso- 
motor nerves  accelerates  the  discharge  of  heat  from  the  surface  of  the  body. 
The  high  temperature  can  be  explained  on  Tscheschichin's  assumption.  The 
lesion  either  stimulates  the  spinal  thermogenic  centers  or  removes  the  influ- 
ence of  the  thermo-inhibitory  centres.  These  clinical  observations  are  the 
strongest  support  which  has  been  found  for  the  belief  in  the  existence  of 
centres  in  the  spinal  cord  which  accelerate  heat  production.  Complete  sec- 
tion of  the  cervical  part  of  the  spinal  cord  in  a  dog  or  rabbit  is,  under  ordi- 
nary conditions,  always  followed  by  a  rapid  fall  of  the  internal  temperature 
and  diminished  oxidation.  These  varying  results  in  man  and  in  animals 
have  been  explained  by  supposing  that  after  section  of  the  cervical  cord,  on 
the  one  hand,  the  discharge  of  heat  is  increased  by  dilatation  of  the  super- 
ficial bloodvessels,  in  consequence  of  vasomotor  paralysis ;  and,  on  the  other 
hand,  the  production  of  heat  is  increased  by  withdrawal  of  thermo-inhibitor}' 

**  Tscheschichin :    Reichert  und  Du  Bois — Reymond's  Archiv,  1866. 


324  CAKTWBIGHT  LECTURES 

cerebral  impulses.  If,  as  ordinarily  happens  in  dogs  and  smaller  animals, 
the  first  factor  predominates  then,  in  consequence  of  sinking  of  the  internal 
temperature,  the  heat-producing  processes  are  so  reduced  that  the  influence 
of  the  second  factor  is  not  manifest.  The  attempt  has  been  made  to  test  this 
explanation  by  placing  the  animal  in  a  warm  atmosphere.  If  thereby  the 
heat  discharge  be  reduced  to  a  minimum,  it  is  found  that  the  internal  tem- 
perature of  the  animal  often  rises  more  rapidly  than  that  of  a  normal  one 
under  the  same  external  conditions.  Here  thermometric  observations  are  not 
conclusive  as  to  the  point  to  be  tested,  for  the  more  rapid  rise  can  be  ex- 
plained simply  by  failure  of  the  heat-regulating  mechanism.  Wood's  calori- 
metric  experiments  seem  to  show  that  there  is  greater  heat  production,  under 
these  circumstances,  in  the  animal  with  cut  cord.  These  experiments  admit 
of  various  interpretations,  but  if  they  be  regarded  as  establishing  the  assump- 
tion from  which  we  started,  then  it  is  evident  that  in  man  and  in  large 
animals  the  increased  heat  production  after  injury  of  the  cord  would  not  he 
60  readily  overcome  by  the  increased  discharge  of  heat  from  the  surface,  for, 
in  proportion  to  its  volume,  a  large  animal  has  less  surface  than  a  small  one. 
The  interplay,  therefore,  of  these  opposing  tendencies  might  cause  different 
results,  according  to  the  size  of  the  animals. 

Tscheschichin  found  that  a  transverse  section  made  at  the  junction  of  the 
pons  and  medulla  oblongata  is  followed,  in  a  short  time,  by  rise  of  internal 
temperature.  As  the  superficial  temperature  is  also  elevated,  he  concludes 
that  there  is  no  retention  of  heat;  moreover  the  section  is  made  above  the 
dominant  vasomotor  centre.  Wood  has  shown  by  means  of  the  calorimeter 
that  after  this  operation  there  is  actual  increase  in  the  production  of  heat. 
He,  as  well  as  Tscheschichin,  interprets  the  experiment  as  indicating  thermo- 
inhibitory  centres  above  the  lower  border  of  the  pons.  Bruck  and  Giinter  " 
repeated  and  modified  these  experiments  under  Heidenhain's  directions. 
Out  of  seven  cases  in  which  they  separated  tlie  pons  from  the  medulla,  they 
observed  in  only  two  rise  of  temperature;  of  eleven  cases  in  which  they  punc- 
tured the  pons  with  a  needle,  in  five  they  noted  increased  temperature. 
Heidenhain  thinks  these  experiments  indicate  heat-exciting  rather  than 
heat-moderating  centres,  and  it  must  be  admitted  that  the  evidence  is  not 
conclusive  in  support  of  either  view. 

By  far  the  most  interesting  and  conclusive  experiments,  showing  the 
influence  of  the  central  nervous  system  on  thermogenesis  are  those  of  Isaac 
Ott,  followed  by  Richet,  Aronsohn  and  Sachs,  Baginsky,  and  Girard."    The 

""Bruck  and  Giinther:    Pfliiger's  Archiv,  Bd.  III. 

"Ott:  Journal  of  Nervous  and  Mental  Diseases,  April,  1884;  Medical  News, 
July,  1885.  Therapeutic  Gazette,  Sept.,  1887.  Richet:  Arch,  de  Phys.,  1884. 
Aronsohn  and  Sachs:  Pfliiger's  Archiv,  Bd.  XXXVII.  Baginsky  and  Lehman, 
Virchow's  Archiv,  Bd.  CVI.    Girard:    Arch,  de  Phys.,  1886. 


GENERAL  PATHOLOGY  OF  FEVER         325 

observations  of  Ott,  Eichet,  and  Aronsohn  and  Sachs  were  made  independ- 
ently and  at  about  the  same  time,  but  Ott  was  the  pioneer.  The  experiments 
of  Aronsohn  and  Sachs  are  reported  with  especial  fulness  and  detail.  These 
investigators  found  that  if  the  skull  of  a  rabbit  be  trephined  at  the  junction 
of  the  coronal  and  sagittal  suture,  and  a  needle  be  passed  vertically  down  so  as 
to  puncture  the  anterior  part  of  the  caudate  nucleus  near  its  median  con- 
vexity, there  follows  a  rise  of  temperature,  which  may  amount  to  three  degrees 
or  more,  and  which  may  persist  for  two  or  three  days.  The  rapidity  and  the 
duration  of  this  elevation  of  temperature  vary  somewhat  with  the  depths  of 
the  puncture,  parts  immediately  beneath  the  caudate  nucleus  being  also 
thermically  active.  Puncture  of  the  overlying  cortex  or  medullar}'  sub- 
stance has  no  such  effect  upon  temperature.  With  the  exception  of  some 
increase  in  the  frequency  of  the  respiration  and  of  the  pulse,  the  animal  after 
puncture  of  the  anterior  median  part  of  the  caudate  nucleus  presents  no 
abnormal  symptom  other  than  the  rise  of  temperature. 

I  have  several  times  repeated  this  experiment  and  always  with  the  result 
described.  That  the  pyrexia  induced  by  puncture  of  the  caudate  nucleus  is 
not  due  to  vasomotor  changes  causing  retention  of  heat,  is  proven  by  Eichet 's 
and  Ott's  calorimetric  experiments,  and  by  the  determination  by  Aronsohn 
and  Sachs  that  the  consumption  of  oxygen  and  the  elimination  of  carbonic 
acid,  and  urinary  nitrogen  are  increased.  Aronsohn  and  Sachs  and  Girard 
find  that  electrical  stimulation  of  the  anterior  median  part  of  the  caudate 
nucleus  causes  the  same  thermic  phenomena  as  the  puncture,  and  they,  there- 
fore, conclude  that  this  region  contains  a  thermo-excitor  heat  centre.  This 
is  the  natural  interpretation  of  their  experiment,  although  Baginsky  and  Ott 
regard  the  centre  as  thermo-inhibitory  on  grounds  which  cannot  be  con- 
sidered convincing. 

Ott  claims  that  there  are  four  cerebral  heat  centres,  one  about  the  corpus 
striatum,  the  second  in  the  caudate  nucleus,  the  third  in  the  anterior  inner 
end  of  the  optic  thalamus  and  the  fourth  near  the  median  line  between  the 
optic  thalamus  and  the  corpus  striatum.  The  greatest  rise  of  temperature  he 
found  after  injury  of  the  thalamic  centre. 

No  adequate  demonstration  has  been  afforded  of  any  influence  of  the 
cerebral  hemispheres  upon  thermogenesis.  Corin  and  van  Beneden  ^  find 
that  pigeons,  after  removal  of  their  cerebral  hemispheres,  exhibit  no  change 
of  temperature,  no  failure  of  the  heat-regulating  mechanism,  and  no  alter- 
ation in  the  excretion  of  carbonic  acid. 

I  have  endeavored  to  present  to  you  the  main  physiological  facts  bearing 
upon  the  relation  of  the  nervous  system  to  thermogenesis.    It  must  be  ad- 

**  Corin  and  van  Beneden:    Arch,  de  Biol.,  1887. 


326  CARTWRIGHT  LECTURES 

mitted  that  we  are  left  to  surmise  as  to  the  interpretations  of  many  of  the 
facts,  and  particularly  as  to  their  connection  with  eacli  other.  But  certain 
important  points  come  out  clearly.  We  have  found  evidence  of  the  existence 
in  the  body  of  chemical  processes  resulting  chiefly  in  the  production  of  heat 
energy.  We  have  learned  that  these  processes  are  under  the  direct  control 
of  the  nervous  system,  and  possibly  of  nerves  distinct  from  those  now  recog- 
nized as  motor  or  secretory.  We  have  seen  that  there  are  regions  in  the 
central  nervous  system  which  are  doubtless  in  some  way  connected  with  these 
nerves,  and  through  them  control  the  chemical  processes  resulting  in  the 
production  of  heat. 

The  bearing  of  these  facts  upon  the  theory  of  fever  is  evident.  The  study 
of  heat  production  and  of  heat  loss  in  fever  has  led  us,  by  arguments  which 
need  not  be  repeated,  to  the  conclusion  that  the  pyrogenic  agent  must  in  some 
way  act  upon  the  heat-regulating  mechanism.  The  study  of  this  mechanism, 
more  particularly  of  its  thermogenic  side,  affords  some  insight  into  the 
manner  in  which  the  fever-producing  agent  may  affect  the  regulation  of  heat. 
The  main  difficulty  in  the  neurotic  theory  of  fever  has  been  to  understand 
how  by  any  action  of  the  fever-producing  agent  directly  upon  the  nervous 
system  the  chemical  processes  leading  to  heat  production  could  be  stimulated. 
I  have  dwelt  thus  at  length  upon  the  innervation  of  thermogenesis  to  show 
that  this  difficulty  has  been  in  great  part  overcome. 

To  some  it  seems  more  reasonable  to  suppose  that  the  pyrogenic  agent 
circulating  in  the  blood  acts  directly  upon  the  tissues,  altering  and  stimu- 
lating their  chemical  changes.  This  is  the  haemic  theory,  which,  in  some 
form,  has  always  stood  over  against  the  neurotic  theory  of  fever.  Although 
it  may  at  first  glance  appear  simpler,  the  haemic  theory  is  really  the  more 
complicated,  for  it  has  already  been  set  forth  that  we  cannot  explain  fever 
simply  by  increased  heat  production,  so  that  even  if  the  primary  effect  of  the 
fever  agent  were  upon  the  heat-producing  processes  there  must  be  a  secon- 
dary influence  upon  the  nervous  system,  for  heat  dissipation  is  no  less  dis- 
turbed than  heat  production. 

If  an  animal  be  thoroughly  curarized  so  that  no  impulses  from  the  nervous 
centres  can  reacli  the  muscles,  the  great  heat  producers,  then  it  is  found  to 
he  impossible  to  produce  febrile  elevation  of  temperature  by  the  injection  of 
pyrogenic  agents.  This  fact,  first  demonstrated  by  Zuntz,  is  justly  held  to 
weigh  heavily  in  favor  of  the  neurotic  theory  of  fever. 

Contrary  to  the  results  of  Murri,"  I  liave  not  been  able  to  induce  rise 
of  temperature  or  check  \t<  fall  by  the  injection  of  pyrogenic  agents  into 
the  jugular  veins  of  dogs  whose  spinal  cords  have  been  cut  in  the  lower 

"Murri:    Teoria  della  Febbra,  Fermo,  1874. 


GENERAL  PATHOLOGY  OF  FEVER         327 

cervical  region.  In  these  experiments  I  have  employed  various  pyrogenie 
agents,  and  especially  pepsin  and  papoid.  One  specimen  of  the  latter  which  I 
used  possessed  very  striking  pyrogenie  properties. 

The  pyrexia  produced  by  puncture  of  the  caudate  nucleus  in  the  manner 
already  described,  possesses  all  of  the  essential  properties  of  fever,  regarded 
as  abnormal  elevation  of  temperature.  In  this  experimental  condition  there 
are  increased  production  of  heat,  increased  dissipation  of  heat,  excessive 
elimination  of  urea  and  of  carbonic  acid,  and  excessive  absorption  of  oxygen. 
The  breathing  and  the  pulse  are  increased  in  frequency.  The  elevation  of 
temperature  (usually  after  a  brief  fall)  begins  within  half  an  hour  after  the 
puncture,  attains  a  febrile  height  and  persists  sometimes  for  days.  As  no 
observations  exist  as  to  the  heat  regulation  of  these  animals,  I  have  made 
experiments  on  rabbits  after  puncture  of  the  caudate  nucleus,  by  placing 
them  in  a  cold  environment  and  in  a  box  heated  to  various  temperatures, 
and  I  find  that  their  power  of  temperature  regulation  is  less  than  that  of 
normal  animals. 

These  animals,  in  a  word,  present  all  of  the  essential  symptoms  of  fever, 
and  I  do  not  know  why  we  should  not  call  the  condition  fever.  If  so,  we  must 
admit  that  injury  to  a  circumscribed  definite  region  of  the  brain  is  capable 
of  causing  fever.  This  experiment,  therefore,  is  of  the  greatest  importance 
in  support  of  the  neurotic  doctrine  of  fever.  It  indicates,  of  course,  that  we 
may  have  fever  of  purely  nervous  origin,  without  any  pyrogenie  agent  in  the 
blood.  This  experimental  evidence  is  supported  by  the  clinical  cases  col- 
lected by  ^Yhite  in  "  Guy's  Hospital  Reports,"  1884.  It  is  to  be  hoped  that 
by  careful  thermometric  study  of  focal  brain  and  cord  lesions  a  more  accu- 
rate idea  may  be  reached  than  is  now  possible  of  the  topography  of  the  ther- 
mically  active  regions  in  the  central  nervous  system  of  man. 

Admitting  the  dependence  of  fever  upon  the  nervous  system,  I  do  not 
regard  as  particularly  profitable  with  our  present  knowledge '  the  discussion 
as  to  whether  febrile  thermogenesis  is  excited  by  the  withdrawal  of  thermo- 
inhibitory  impulses  or  by  the  stimulation  of  thermo-excitory  nerves  or  nerve 
centres.  If  we  regard,  and  there  are  forcible  arguments  for  doing  so,  possible 
heat-inhibitory  nerves  as  anabolic,  and  the  heat-exciting  nerves  as  katabolic, 
then  inasmuch  as  the  formative  or  anabolic  processes  are  manifestly  in 
abeyance  in  fever,  we  can  reasonably  infer  that  the  function  of  the  heat 
inhibitory  nerves  or  centres  is  impaired.  The  phenomena  of  the  febrile  chill 
in  which  both  the  contractile  and  the  thermogenic  properties  of  muscle  are 
stimulated,  speak  strongly  in  favor  of  direct  irritation  of  the  heat-exciting 
nerves  in  fever.  We  might  infer,  therefore,  that  both  sets  of  nerves  or  nerve 
centres  are  affected. 


328  CARTWEIGHT  LECTURES 

But  my  aim  in  this  lecture  has  been  not  so  much  to  construct  a  theory  of 
fever,  a  theory  which,  although  it  may  be  useful,  must  necessarily  be  largely 
speculative  if  it  be  coherent  and  rounded  but  to  bring  before  you  the  main 
facts  concerning  heat  production,  heat  loss,  and  heat  regulation  in  fever, 
and  to  point  out  tlie  physiological  basis  on  which  their  solution  is  to  be 
expected. 

Lecture  II 

THE  EFFECTS  OF  INCREASED  TEMPFJRATURE  OF  THE  BODY 

In  the  last  lecture  I  endeavored  to  bring  before  you  the  main  facts  which 
we  possess  bearing  upon  the  explanation  of  febrile  rise  of  temperature. 
After  a  review  of  our  knowledge  concerning  heat  production,  heat  dissipa- 
tion, and  heat  regulation  in  fever,  we  were  led  to  the  conclusion  that  neither 
the  changes  hitherto  observed  in  the  production  of  heat  nor  those  in  the 
loss  of  heat  suffice  to  explain  febrile  temperatures.  Such  an  explanation 
seemed  possible  only  upon  the  assumption  that  the  fever-producing  agents 
act  either  directly  or  indirectly  upon  the  nervous  mechanism  controlling  the 
relations  to  each  other  of  the  production  and  the  discharge  of  heat.  We 
then  turned  our  attention  to  the  relations  of  the  nervous  system  to  these 
processes,  and  found  that  the  investigations  of  recent  years  have  enabled  us 
to  obtain  a  much  clearer  conception  tlian  was  formerly  possible,  of  the  man- 
ner in  which  the  complicated  heat  relations  in  fever  may  be  brought  about 
by  an  action  upon  the  nervous  system.  We  fomid  even  substantial  experi- 
mental basis  in  support  of  clinical  facts  which  show  that  circumscribed 
lesions  of  certain  parts  of  the  central  nervous  system  may  induce  directly 
febrile  disturbances  of  animal  heat. 

To  carry  the  subject  further,  to  consider  whether  pyrogenic  agents  act 
primarily  or  only  secondarily  ujwn  the  processes  concerned  in  heat  produc- 
tion or  upon  tliose  concenied  in  heat  dissipation,  or  upon  the  apparatus 
regulating  tlie  relations  to  each  other  of  these  two  sets  of  processes,  to  dis- 
cuss whether  these  agents  act  directly  upon  the  central  nervous  system,  and 
if  so  upon  what  part;  or  upon  the  peripheral  nerves  or  their  terminations, 
or  upon  the  tissues ;  to  follow  out  more  fully  than  we  have  done  hitherto  the 
themes  here  suggested  would  lead  us  with  our  present  knowledge  into  a  sea 
of  speculation.  We  should  find  only  here  and  there  a  faint  light  of  fact  to 
guide  us.  Even  upon  foundations  as  insecure  as  this  speculations  have  their 
legitimate  uses.  A  good  hypothesis  is  a  most  valuable  incentive  to  scientific 
work.  It  is  not  my  purpose,  however,  to  carry  you  with  me  furtiier  in  this 
direction,  although  I  realize  that  a  single  lecture  has  been  far  from  sufficient 
for  a  thorough  exposition  of  this  subject. 


GENERAL  PATHOLOGY  OF  FEVER         329 

After  dismissing  the  consideratious  bearing  upon  the  so-called  theory  of 
fever,  there  still  remains  a  host  of  questions  properly  belonging  to  our  sub- 
ject. It  is  evidently  impossible,  even  if  it  were  desirable,  that  these  lectures 
should  include  a  discussion  of  all  of  these  questions,  I  have,  therefore, 
selected  certain  ones,  partly  because  they  seem  to  me  of  immediate  interest 
and  partly  because  I  have  given  some  attention  to  their  study. 

In  the  present  lecture  I  wish  to  present  to  you  some  observations  concern- 
ing the  relation  of  elevation  of  temperature  to  other  disorders  of  fever,  and 
as  to  the  question.  How  far  increased  temperature  is  a  source  of  danger 
in  fever? 

Here  I  may  repeat  that  the  word  fever  is  used  as  a  convenient  name  for  a 
group  of  symptoms  conmionly  associated  together  in  febrile  diseases.  The 
association  of  these  symptoms,  however,  is  so  loose  that  we  regard  only  the 
dominant  one — the  increased  temperature — as  the  essential  criterion  of  the 
existence  of  fever.  It  saves  circmnlocution  to  adopt  this  somewhat  vague 
and  common  signification  of  the  term  fever,  although  I  think  it  would  be  an 
improvement  to  confine  the  term  to  abnormal  elevation  of  temperature.  The 
literature  of  fever  is  full  of  misapprehensions  resulting  from  the  various 
meanings  attached  to  the  word  by  different  authors. 

All  of  the  bodily  functions  may  be  disordered  in  fevers.  The  various 
symptoms  or  classes  of  symptoms  which  are  so  commonly  associated  as  to 
be  regarded  by  many  as  belonging  to  the  febrile  process  are,  in  addition  to 
heightened  temperature,  increased  frequency  of  the  pulse  and  other  circu- 
latory disturbances,  increased  rapidity  of  respiration,  muscular  weakness, 
lessened  secretions,  disordered  nutrition  and  digestion,  and  nervous  symp- 
toms. 

What  is  the  connection,  if  any,  between  these  symptoms  and  the  elevation 
of  temperature?  What  degrees  of  elevated  temperature  are  dangerous  to 
life,  and  in  what  does  the  danger  consist?  This  subject  can,  at  least,  claim 
the  interest  that  attaches  to  the  questions  of  the  day.  The  various  opinions 
which  have  been  held  by  clinicians  on  these  points  are  too  well  known  to  you 
to  require  an  historical  review.  I  need  only  remind  you  that  until  within 
a  few  years  the  views  advocated  with  especial  force  for  nearly  thirty  years 
by  Liebermeister  have  prevailed,  although  not  without,  considerable  opposi- 
tion. According  to  these  views,  the  chief  source  of  danger  in  uncomplicated 
essential  fevers  is  the  elevation  of  temperature,  and  the  main  indication  for 
treatment  is  the  reduction  of  temperature.  Above  all,  it  was  urged  with 
apparently  convincing  arguments  that  the  weakness  of  the  heart,  which  is 
undoubtedly  one  of  the  gravest  dangers  of  fevers,  is  the  direct  effect  of  pro- 
longed higli  temperature,  and  is  manifested  anatomically  by  parenchymatous 
or  fatty  degeneration  of  the  cardiac  muscle.  Liebermeister  sharply  defined 
24 


330  CAETWEIGHT  LECTUEES 

his  position  when  he  said,  "  A  man  whose  temperature  measures  continu- 
ously 104°  (40°  C.)  or  more  surely  dies  in  consequence  of  the  elevation  of 
temperature,  one  in  a  few  days,  another  after  a  somewhat  longer  time, 
according  to  the  resistance  of  the  individual."  "  If  his  temperature  reaches 
108.5°  (42.5°  C.)  or  more,  then  is  he  irrecoverably  lost."'" 

At  the  present  moment  there  is  a  decided  reaction  against  these  views,  a 
reaction  which  in  some  quarters  goes  to  the  extent  not  only  of  denying  that 
there  is  danger  in  febrile  temperatures  which  do  not  exceed  a  ver\-  high  point, 
but  of  asserting  that  the  elevation  of  temperature  is  a  beneficient  provision, 
a  most  important  vis  medicatrix  naturae,  which  should  not  be  checked  by  the 
interference  of  the  physician.  This  reaction  of  opinion  is  plainly  due,  in 
great  part,  to  the  disappointment  which  has  followed  the  high  hopes  raised 
by  the  discovery  of  a  number  of  drugs  which  are  admirable  antithermic 
agents  and,  nevertheless,  do  not  exert  over  febrile  diseases  that  controlling 
influence  which  had  been  anticipated. 

These  questions,  you  may  say,  are  clinical  ones,  and  not  much  edification 
is  to  be  expected  from  their  discussion  by  a  pathologist.  So  far  as  the  pro- 
priety of  the  use  of  antipyretic  agents  or  of  any  other  mode  of  treatment  in 
fever  is  concerned,  it  is  true  that  the  decision  must  be  reached  at  the  bedside 
and  cannot  and  never  should  be  controlled  by  the  results  of  experimental 
pathology.  But  an  appeal  has  properly  been  made  to  experimental  path- 
ology to  shed  light  upon  such  questions  as  the  effects  of  heat  upon  the  func- 
tions of  the  whole  body  and  of  its  various  organs,  and  upon  the  causes  of 
parenchymatous  and  fatty  degenerations.  The  arguments  advanced  in  sup- 
port of  the  view  that  all  of  the  characteristic  symptoms  of  fever  are  directly 
dependent  upon  the  increase  of  temperature  and  that  high  temperature  is 
the  chief  source  of  danger,  are  derived  no  less  from  experimental  pathology 
than  from  clinical  observations. 

Three  methods  have  been  employed  to  determine  the  effects  of  increased 
temperature  in  fever:  one  is  to  study  the  effects  of  external  heat  upon  man 
and  animals;  the  second  is  to  examine  in  different  fevers  and  in  different 
cases  of  the  same  fever  the  relation  of  the  temperature  to  the  other  symptoms, 
and  to  the  general  condition  of  the  patient;  and  the  third  is  to  note  the 
influence  of  reduction  of  temperature  upon  these  symptoms.  Each  method 
has  its  limitations. 

The  condition  produced  by  exposure  to  external  heat,  even  if  it  be  called 
thermic  fever,  is  something  quite  different  from  ordinary  fevers,  and  we 
cannot  transfer  the  results  obtained  by  this  method  directly  to  the  explana- 
tion of  febrile  phenomena.  On  the  other  hand,  in  the  clinical  study  of  fevers 
it  is  very  difficult  and  often  an  arbitrary  matter  to  separate  the  effects  of  in- 

*•  Liebermeister:  Volkmann's  Sammlung,  No.  31,  p.  240. 


GENERAL  PATHOLOGY  OF  FEVER         331 

creased  temperature  from  those  of  other  factors  nearly  always  present. 
Hence  we  find  no  agreement  of  opinion  among  physicians  as  to  what  symp- 
toms or  lesions  in  fever  are  referable  to  the  heightened  temperature,  and  what 
are  due  to  infectious  or  other  conditions  often  present.  Even  the  frequent 
or  constant  association  of  certain  symptoms  ^vith  elevated  temperatures  and 
their  subsidence  or  disappearance  by  reduction  of  temperature  do  not  justify 
us  in  inferring  that  the  high  temperature  is  the  cause  of  the  symptoms,  for 
both  may  be  coordinate  effects  of  the  same  cause,  and  the  so-called  antipyretic 
treatment  may  influence  other  conditions  as  well  as  the  temperature.  As 
has  been  frequently  said  of  late,  the  high  temperature  may  be  rather  an  index 
of  the  severity  of  the  disease  than  a  source  of  danger  in  itself. 

In  hyperpyrexia  and  in  many  cases  of  insolation  there  can  be  no  doubt 
that  the  high  temperatures,  as  such,  are  the  main  elements  of  danger.  But 
both  of  these  conditions  liave  impoi-tant  points  of  distinction  from  ordinary 
febrile  processes.  In  hyperpyrexia  there  is  probably  almost  complete  paral- 
ysis of  heat  regulation,  and  Ave  shall  find  that  an  analogous  condition  with 
similar  dangers  sometimes  develops  in  animals  artificially  heated.  The 
cases  of  insolation  in  which  the  high  temperature  is  so  dangerous  are  analo- 
gous to  the  condition  which  may  be  produced  in  animals  by  brusque  elevation 
of  the  bodily  temperature  through  exposure  to  heat,  and  which  differs  from 
that  resulting  from  more  gradual  increase  of  temperature. 

The  most  direct  way  of  determining  the  influence  of  heat  upon  the  body 
is  to  raise  the  internal  temperature  by  the  external  application  of  heat. 
Here  we  are  not  disturbed  by  the  presence  of  other  factors,  such  as  infection, 
which  render  doubtful  so  many  of  the  conclusions  derived  from  clinical 
observations  as  to  the  effects  of  high  temperatures.  For  the  solution  of  many 
problems  it  is  evidently  irrelevant  whether  the  source  of  heat  be  within  or 
without  the  body. 

These  experiments,  if  properly  conducted,  are  calculated  to  shed  much 
light  upon  many  questions  relating  to  the  effects  of  febrile  temperatures. 

According  to  the  testimony  of  all  experimenters,  a  mammalian  animal, 
artificially  heated,  dies  when  its  internal  temperature  reaches  111.2°  F. 
(44°  C.)  or  113°  F.  (45°  C).  Death  is  preceded  by  convulsions  and  imme- 
diately or  soon  after  death  rigor  mortis  appears.  At  the  moment  of  death 
the  irritability  of  the  heart  and  muscles  ceases.  Death  seems  to  be  due  to 
heart  paralysis,  and  the  cause  of  this  is  usually  set  down  as  heat  rigor,  but 
this  is  not  probable  as  death  generally  occurs  at  a  temperature  several  degrees 
below  that  at  which  rigor  of  the  heart  muscles  appears. 

It  is  generally  argued  that  temperatures  several  degrees  below  those  which 
are  fatal  must  exert  toxic  effects,  and  this  conclusion  seemed  to  be  substan- 
tiated by  the  majority  of  experimenters,  who  found  that  animals  whose  tem- 


332  CARTWKIGHT  LECTURES 

peratures  were  artificially  raised  to  105°  F.  (40.5°  C.)  or  107°  F.  (41.7°  C), 
or  even  to  a  lower  point,  manifested  signs  of  illness.  These  latter  results, 
however,  are  opposed  to  those  obtained  by  Rosenthal,  and  especially 
Nauuyn,"  who  points  out  that  the  conditions  in  most  previous  experiments 
were  not  favorable,  as  the  animals  were  generally  placed  in  small,  dark, 
poorly  ventilated  metallic  boxes.  Naunyn  succeeded  in  keeping  a  rabbit 
alive  for  thirteen  days  with  an  average  temperature  of  106.7°  F.  (41.5°  C). 

Following  Namiyn's  example,  I  have  had  constructed  a  wooden  box,  three 
feet  long,  two  feet  high,  and  two  feet  broad,  which  fits  closely  within  a  double- 
walled  galvanized  iron  box.  The  wooden  box  is  provided  with  a  perforalou 
movable  bottom,  which  allows  the  urine  to  escape.  The  space  between  the 
two  walls  of  the  iron  l)0x  measures  three  inches  across,  and  is  filled  with 
water,  which,  therefore,  surrounds  the  inner  box  on  all  sides,  except  at  the 
top,  which  is  left  open.  The  dimensions  of  this  apparatus  are  somewhat 
larger  than  those  of  Naunyn's  heating-box.  A  folded  woollen  blanket  was 
drawn  over  each  end  of  the  box,  so  as  to  leave  uncovered  at  least  one-third, 
and  generally  more  of  the  top.  A  rose  burner  placed  underneath  served  to 
heat  the  box.  At  first  a  thermo-regulator  was  employed,  but  this  was  found 
unnecessary,  as  the  temperature  of  the  room  varied  but  little,  and  there  was 
no  difficulty  in  keeping  a  sufficiently  constant  temperature  in  the  box.  The 
experiments  were  made  upon  rabbits,  and  only  a  single  one  was  placed  in 
the  box  at  a  time.  Corrected  thermometers  were  used.  The  temperature 
of  the  box  was  taken  a  short  distance  above  the  bottom,  and  that  of  the  rabbit 
at  a  depth  of  three  to  four  inches  in  the  rectum.  This  occasion  does  not  seem 
an  appropriate  one  to  describe  these  experiments  in  detail  with  their  pro- 
tocols. I  shall  take  another  opportunity  for  that,  and  at  present  give  only  a 
general  account  of  those  results  which  relate  to  the  subject  before  us. 

In  the  box  described  I  have  succeeded  in  keeping  for  three  weeks  two  large 
black  rabbits,  the  one  with  an  average  rectal  temperature  of  107.3°  F. 
(41.8°  C),  the  other  with  an  average  temperature  of  106.6°  F.  (41.4°  C). 
The  rectal  temperature  fluctuated  usually  between  105.5°  F.  (40.8°  C.) 
and  108°  F.  (42.2°  C),  scarcely  ever  sinking  below  105°  F.  (40.5°  C),  but 
occasionally  rising  as  high  as  109.5°  F.  (43.1°  C).  The  temperature  of  the 
box  varied  between  96°  F.  (35.5°  C.)  and  106°  F.  (41.1°  C).  The  rabl)iis 
lay  most  of  the  time  stretched  out,  breathing  very  rapidly.  They  took  their 
food  greedily,  and  did  not  appear  ill.  At  the  end  of  the  experiment  the  first 
animal  was  removed  from  the  box,  and  appearing  perfectly  well  for  ten  days 
afterward  it  was  used  for  another  experiment;  the  second  animal  was  killed 
at  the  end  of  the  experiment,  and  presented  marked  fatty  degeneration  of 

"Rosenthal:  Zur  Kenntniss  der  Warmeregulirung  u.  s.  w.,  Erlangen,  1872. 
Naunyn:   Archiv  f.  exp.  Path.  u.  Pharm.,  Bd.  18. 


GENERAL  PATHOLOGY  OF  FEVER         333 

the  heart,  liver,  and  kidneys.    Both  animals  lost  weight  while  in  the  box. 

In  these  and  similar  experiments  the  rabbits  were  given  only  moist,  green 
fodder,  and  were  allowed  to  drink  plenty  of  water,  which  they  took  eagerly. 
It  is  important  for  the  success  of  the  experiment  that  the  temperature  should 
be  gradually,  and  not  suddenly,  raised. 

Different  rabbits  offer  varying  degrees  of  resistance  to  the  effects  of  high 
external  temperature.  It  has  seemed  to  me  that  black  and  gray  rabbits 
surpass,  in  this  respect,  white  rabbits.  The  same  temperature  of  the  box 
does  not  produce,  in  all  cases,  the  same-  rectal  temperature  in  different 
animals,  or  in  the  same  animal  at  different  times.  No  factor  is  of  more 
importance  in  determining  the  effects  of  external  heat  than  the  animal's 
power  of  temperature  regulation.  Failure  of  this  power  is  manifested  by  a 
sudden  rise  of  internal  temperature,  which  may  quickly  attain  a  point  in- 
compatible with  life.  This  event  may  take  place  without  any  alteration  in 
the  box  temperature.  The  degree  of  internal  temperature  at  which  this 
paralysis  of  heat  regulation  occurs  varies  in  different  animals.  One  may  be 
able  to  hold  his  temperature,  for  a  short  time,  from  further  rise  at  as  high  a 
point  as  109.5°  F.  (43.1°  C.)  ;  in  another,  after  the  temperature  has  reached 
107.6°  F.  (41.5°  C),  there  may  occur,  without  any  change  in  the  box  tem- 
perature, a  sudden,  and  often  fatal,  elevation  of  temperature.  In  general, 
temperatures  between  108°  F.  (42.2°  C.)  and  109°  F.  (42.8°  C.)  may  be 
regarded  as  critical  temperatures  for  tliese  animals.  One  is  forcibly  re- 
minded by  these  sudden  and  dangerous  elevations  of  temperature  of  the 
occurrence  of  hyperpyrexia  in  certain  fevers  of  human  beings,  and  there  is 
reason  to  believe  that  this,  too,  is  caused  by  paralysis  of  heat  regulation. 

It  seemed  to  me  of  some  practical  interest  to  determine  what  effect  upon 
the  rabbit's  power  of  resisting  high  temperature  is  exerted  by  exhausting 
influences,  particularly  by  anaemia.  For  this  purpose  rabbits  which  had 
been  moderately  bled,  and  others  which  had  been  used  for  some  other  experi- 
ments, were  placed  in  the  hot  box.  It  was  found  that  these  animals  are, 
although  not  without  occasional  exceptions,  unmistakably  less  resistant  to 
the  effects  of  high  temperatures  than  are  robust  animals.  They  succumb 
sooner,  and  at  lower  box  temperatures. 

We  may  now  consider  what  inferences  may  be  drawn  from  these  and 
similar  experiments  as  to  the  effects  of  high  bodily  temperatures.  It  seems 
clear  that  a  considerable  part  of  the  current  arguments  based  upon  experi- 
ments concerning  tlie  injurious  effects  of  high  temperatures  must  be  revised 
in  the  light  of  Naunyn's  experiments,  and  of  those  which  I  have  briefly 
related.  Because  an  animal  may  be  killed  by  raising  its  temperature  to 
111°  F.  (43.9°  0.),  or  113°  F.  (45°  C),  it  does  not  follow  that  an  increase 
of  temperature  up  to  within  4°  or  5°  F.  of  this  fatal  point  involves  danger 


334  CARTWRIGHT  LECTURES 

to  life,  or  even  any  serious  disturbance  of  the  functions  of  the  body.  Al- 
thouo-h  experiments  in  hot-air  chaml)ers  show  that  in  man  brusque  elevations 
of  the  temperature  by  only  a  few  degrees  give  rise  to  serious  symptoms, 
Krishaber"  found  that  by  habituation  his  temperature  could  be  raised  to 
10G.5°  F.  (41.4°  C),  or  107.2°  F.  (41.8°  C),  without  much  discomfort. 
As  small  animals  generally  succumb  more  readily  than  large  ones  to  artificial 
heating,  it  is  not  likely  that  the  power  of  resistance  in  human  beings  is  less 
than  that  found  to  exist  in  rabbits,  and  there  is  reason  to  believe  that  it  is 
greater. 

We  cannot  transfer  directly  to  human  beings  the  highest  temperature  at 
which  we  found  rabbits  can  exist  without  serious  discomfort  save  increased 
respiration.  A  rabbit's  temperature  is  normally  considerably  higher  than 
that  of  man,  and  apparently  slight  causes  suffice  to  produce  marked  fluctua- 
tions. The  normal  rectal  temperature  of  the  rabbits  used  in  my  experiments 
was  generally  between  102°  F.  (38.9°  C.)  and  103°  F.  (39.4°  C).  The 
highest  average  temperature  at  which  a  rabbit  was  kept  for  three  weeks  in 
the  hot  box  exceeded,  therefore,  by  4°  to  5°  F.  the  average  normal  tempera- 
ture. Such  an  increase  would  not  correspond  to  a  high  febrile  temperature 
in  man.  We  can,  however,  with  equal,  and  probably  greater  propriety,  com- 
pare this  temperature  with  that  at  which  death  surely  occurs  in  a  condition 
bordering  on  heat  rigor.  This  temperature  (111°  to  113°  F.)  is  probably 
about  the  same  for  man  as  for  rabbits  and  other  mammalians.  From  this 
point  of  view  the  inference  may  be  drawn,  although,  of  course,  with  much 
reserve,  that  human  beings  may  tolerate  temperatures  of  107°  F.  (41.7°  C), 
or  even  higher,  for  a  considerable  time.  This  inference  is  supported  by  clini- 
cal observations,  especially  in  cases  of  relapsing  fever. 

As  already  pointed  out,  the  condition  produced  by  artificial  heating  is 
not  directly  comparable  with  that  in  fever.  In  the  former  the  loss  of  heat 
from  the  body  is  reduced  to  a  minimum;  the  superficial  temperature  is 
three  or  more  degrees  higher  than  the  internal,  so  that  the  average  temper- 
ature of  tlie  whole  body  is  higher  than  in  fever  with  the  same  internal  tem- 
perature. We  cannot  say,  therefore,  but  that  man  may  tolerate  considerably 
higher  internal  temperatures  when  the  elevation  is  brought  about  under 
conditions  in  which  the  discharge  of  heat  is  not  checked  than  when  the 
temperature  is  forced  up  by  stopping  heat  dissipation.  This  would  be 
proven  if  confidence  could  be  placed  in  the  enormous  elevations  of  tempera- 
ture reported  by  Teale  and  others.  In  these  cases,  however,  even  if  authenti- 
cated, it  is  probable  that  heat  is  abnormally  distributed  in  the  body,  and  we 
cannot  infer  that  the  internal  temperature  is  uniformly  raised  to  such  para- 
doxical heights. 

-'Krishaber:    Gaz.  MM.  de  Paris,  1877. 


GENERAL  PATHOLOGY  OF  FEVER         335 

It  is  of  the  utmost  importance  to  bear  in  mind  that,  as  my  experiments 
have  showTi,  not  only  do  animals  differ  in  their  power  of  tolerating  high 
temperatures  of  the  body,  but  this  resistance  may  be  weakened  by  various 
depressing  causes.  Nothing  would  be  more  irrational  than  to  conclude, 
because  one  individual  in  a  certain  condition  can  tolerate  very  high  tempera- 
tures, another  in  a  different  condition  possesses  the  same  power.  In  fevers 
we  have  various  factors,  particularly  infection,  which  we  may  well  believe 
can  lower  tlie  tolerance  of  high  temperatures.  That  in  some  fevers,  par- 
ticularly relapsing  fever,  this  does  not  appear,  or  only  partially,  does  not  dis- 
prove that  in  another  fever,  such  as  typhoid  or  pneumonia,  the  system  may 
be  placed  ])y  other  factors  of  the  disease  in  such  a  condition  that  even 
moderately  high  temperatures  are  injurious.  It  does  not  seem  to  me  proper 
in  these  cases  to  lay,  as  some  seem  inclined  to  do,  the  sole  stress  upon  the 
element  of  infection.  This  is  in  all  likelihood  the  determining  factor,  but 
the  practitioner  cannot  shut  his  eyes  to  the  possibility  that  under  its  influ- 
ence the  high  temperature,  as  such,  is  a  source  of  danger  to  his  patient. 

^yith  these  restrictions  I  shall  surely  not  be  misunderstood  when  I  assert 
that  temperatures  which  are  ranked  as  high  febrile  temperatures  do  not  in 
themselves,  independently  of  other  factors,  exert  any  such  injurious  influ- 
ence as  has  been  usually  attributed  to  them. 

Our  attention  up  to  this  point  has  been  directed  to  the  effects  of  high 
temperatures  upon  the  general  condition  of  the  body.  It  is  of  importance 
for  the  proper  understanding  of  fever  to  determine  the  influence  of  heat 
upon  the  structure  and  functions  of  the  various  organs.  To  what  extent 
can  the  febrile  disorders  of  respiration,  of  circulation,  of  secretion,  of  nutri- 
tion, of  innervation  be  attributed  directly  to  the  elevated  temperature? 
These  are  questions  which  can  be  answered  better  by  experimental  methods 
than  by  clinical  observation,  for  the  latter  has  to  deal  with  the  effects  of  heat 
complicated  by  other  circumstances  whose  influence  cannot  be  accurately 
determined.    The  one  method,  however,  should  be  made  to  control  the  other. 

The  most  striking  immediate  effect  of  heat  upon  an  animal  is  increased 
frequency  of  respiration.  When  a  dog  or  a  rabbit  is  placed  in  an  atmosphere 
of  100°  F.  (37.8°  C),  it  at  once  begins  to  pant  and  the  respiration  may  run 
up  to  150°  or  more.  The  causation  of  this  increased  respiration,  to  which 
the  name  heat  dyspnoea  has  been  applied  by  Ackermann,"  has  been  re- 
peatedly investigated.  Goldstein  "  in  Fick's  laboratory  found  that  by  apply- 
ing to  the  carotid  arteries  tubes  through  which  hot  water  is  flowing  the 
respirations  may  be  greatly  increased  in  frequency.  Goldstein's  experiment 
is  usually  cited  as  the  crucial  one,  showing  that  the  increased  breathing  is 

*'  Ackermann:    Deutsches  Archiv  f.  klin.  Med.,  Bd.  II. 
^'Goldstein:    Wiirzburger  Verhandl.,  1871. 


336  CARTWRIGHT  LECTURES 

due  to  the  effect  of  the  heated  blood  upon  the  respiratory  centres  in  the 
medulla  oblongata.  Sihler,"  working  in  the  Biological  Lalwratory  of  the 
Johns  Hopkins  University,  however,  has  demonstrated  that  the  increased 
respiration  of  an  animal  exposed  to  heat  is  due  to  two  causes,  warmed  blood 
and  stimulation  of  the  skin  by  the  heat,  and  that  probably  skin  stimulation 
is  the  more  important  factor.  Some  of  Sihler's  criticisms  of  Goldstein's  ex- 
periments have  been  met  by  Gad  and  von  Mertschinsky  '*  who  have  made  it 
evident  that  increased  temperature  of  the  blood  stimulates  the  respiratory 
centres,  or  increases  their  irritability.  Section  of  the  vagi  does  not  check 
heat  dyspnoea,  so  that  this  does  not  result  primarily  from  the  action  of  the 
increased  temperature  upon  the  terminal  pulmonary  expansion  of  these 
nerves.  The  removal  of  afferent  impulses  form  the  skin  by  section  of  the 
spinal  cord  does,  however,  exert  so  marked  an  influence  that  it  cannot  be 
doubted  that  heat  stimulation  of  the  skin  is  an  important  element  in  the 
causation.  I  have  convinced  myself  of  the  correctness  of  Sihler's  explanation 
by  observing  that  in  the  hot  box  at  temperatures  of  90°-95°  F.  (33.2°-35°  C.) 
rabbits  often  preserve  their  normal  temperature,  and  still  their  breathing 
is  markedly  increased,  and  that,  on  the  other  hand,  upon  taking  them  out 
of  the  box  the  respirations  may  sink  before  the  internal  temperature  begins 
to  fall.  In  one  striking  experiment  the  respirations  fell  immediately  to 
about  normal  upon  removing  from  the  hot  box  a  rabbit  whose  skull  had  been 
trephined  on  each  side  of  the  median  line,  and  the  optic  thalami  punctured 
with  a  needle. 

We  cannot  transfer  directly  to  human  beings  tlie  results  of  experiments 
on  heat  dyspnoea  in  animals,  because  in  the  latter  respiration  has  a  far  more 
important  function  in  temperature  regulation  than  in  the  former.  To  keep 
cool  a  dog  pants  under  circumstances  when  a  man  sweats.  As  heat  regulation 
is  largely  influenced  by  the  cutaneous  temperature,  it  is  not  improbable  that 
in  man  heat  stimulation  of  the  skin  is  less  prominent  tlian  the  warmed  blood 
acting  upon  the  respiratory  centres  in  increasing  the  frequency  of  respira- 
tion in  fever. 

Inasmuch  as  disturbances  of  the  heart  and  of  the  circulation  in  general 
are  among  the  most  important  symptoms  of  fever  it  is  natural  that  much 
attention  should  have  been  given  to  the  study  of  the  effects  of  heat  upon  the 
organs  of  circulation.  The  supposed  injurious  effects  of  prolonged  high 
tem|K'ratures  in  fever  have  been  usually  attri})uted  especially  to  some  toxic 
action  of  heat  upon  the  heart. 

*  Sihler:  Journal  of  Physiology,  II,  and  Studies  from  the  Biological  Laboratory, 
Johns  Hopkins  University,  Baltimore,  II. 

'"Cad  and  v.  Mertschinsky:  Virchow  u.  Hirsch's  Jahresbericht,  1881,  Bd.  I, 
S.  197. 


GENERAL  PATHOLOGY  OF  FEVER         337 

That  the  pulse-rate  is  quickened  by  artificially  heating  rabbits  and  dogs 
has  long  been  known.  The  positive  demonstration  that  this  acceleration  is 
due  to  the  direct  action  of  the  heated  blood  upon  the  mammalian  heart  itself 
was  first  given  by  my  colleague,  Prof.  Martin."  By  conducting  through  the 
dog^s  heart,  isolated  physiologically  by  the  ingenious  method  which  he  de- 
vised, Martin  proved  that  the  heart  "beats  quicker  when  supplied  with 
warm  blood  and  slower  when  cold  blood  is  supplied  to  it ;  also,  that  the  rate 
of  beat  depends  much  more  upon  the  temperature  of  the  blood  in  the  coron- 
ary arteries  than  on  its  temperature  in  the  right  auricle  or  ventricle." 
These  experiments  make  it  unnecessary  to  recur  to  any  action  of  the  heated 
blood  upon  extrinsic  cardiac  nerves  or  nerve  centres  in  order  to  explain  the 
quickened  pulse  of  fever.  Moreover,  Fick  "*  found  that  the  nervous  centres 
of  the  heart  and  bloodvessels  are  unaffected  by  heating  the  blood  flowing 
through  the  carotid  arteries  iji  the  manner  adopted  by  Goldstein  in  his  ex- 
periments on  heat  dyspnoea. 

Prof.  Martin  has  kindly  permitted  me  in  this  connection  to  mention  cer- 
tain unpublished  results  of  experiments  which  he  is  now  conducting  upon 
the  effects  of  heat  and  cold  on  the  isolated  heart.  As  these  results  are  perti- 
nent to  our  subject  I  gladly  avail  myself  of  this  privilege.  The  table  of  an 
experiment  which  I  have  examined  shows  that  the  isolated  cat's  heart  beats 
regularly  and  more  and  more  rapidly  as  the  temperature  of  the  blood  is 
gradually  raised  to  111.2°  F.  (4-1°  C).  At  this  point  the  beats  become 
irregular,  but  are  restored  to  their  normal  rhythm  by  feeding  the  heart  with 
cooler  blood.  The  temperature  of  about  111°  F.  (43.9°  C.)  appears  to  be 
a  critical  one  for  the  isolated  heart.  Above  111.2°  (44°  C.)  to  113° 
(45°  C.)  the  pulsations  become  slower  instead  of  quicker  as  the  temperature 
is  raised.  At  122°  F.  (50°  C.)  the  heart's  action  ceased,  but  the  heart  was 
made  to  beat  again  by  supplying  it  with  cooler  blood,  showing  that  the 
cessation  was  not  due  to  heat  rigor.  This  interesting  experiment  teaches 
among  other  things  that  very  high  temperatures  may  produce  results  differ- 
ing not  only  in  degree  but  also  in  kind  from  those  of  temperatures  only  a 
degree  or  two  lower. 

We  may  consider  it  then  established  that  increased  frequency  of  the  pulse 
in  fever  is  referable  to  the  direct  action  of  the  warmer  blood  on  the  nervo- 
muscular  substance  of  *Jie  heart  itself.  Clinical  observation  of  cases  of  fever 
makes  it  evident  that  there  may  be  and  often  are  present  other  circumstances 
which  influence  the  rapidity  of  the  heart's  pulsations,  circumstances  which 

"  Martin:  The  Direct  Influence  of  Gradual  Variations  of  Temperature  upon  the 
Rate  of  Beat  of  the  Dog's  Heart,  Philosophical  Transactions  of  Royal  Society, 
part  II,  1883. 

^Fick:    Pfliiger's  Archiv,  Bd.  V. 


338  CARTWRIGHT  LECTURES 

in  themselves  may  slow  or  may  quicken  the  pulse.  Large  series  of  statistics, 
therefore,  are  required  to  bring  out  the  ratio  between  the  pulse-rate  and  the 
temperature  in  fever  and  even  then  for  any  given  temperature  the  maximum 
and  the  minimum  pulse-rates  lie  so  far  apart  that  the  statement  of  the 
average  increase  in  the  frequency  of  the  pulse  for  each  degree  of  rise  of 
temperature,  such  as  has  been  computed  by  Liebermeister,  has  very  little 
value. 

Not  only  is  the  pulse-rate  quickened  in  fever,  but  tliere  are  often  other 
and  more  serious  circulatory  disturbances.  In  the  fever  produced  in  rabbits 
by  injection  of  the  swine  plague  bacillus  I  find  a  reduction  of  the  blood- 
pressure  measured  in  the  carotid  artery,  and  others  have  obtained  similar 
results  in  the  artificial  fevers  of  animals.  The  determination  of  the  blood- 
pressure  in  fevers  of  human  beings  by  means  of  Basch's  sphygmomanometer 
has  given,  in  the  hands  of  different  experimenters '"  such  contradictory 
results,  that  no  conclusion  can  be  drawn,  unless  it  be  the  very  probable  one 
that  the  blood-pressure  varies,  being  sometimes  high,  sometimes  low,  and 
sometimes  normal  in  fever.  That  the  arterial  tension  is  often  reduced  is 
made  evident  by  the  marked  dicrotism  of  the  pulse  wave.  This  dicrotism, 
however,  characterizes  particularly  septic  and  typhoid  types  of  fever  and  is 
absent  during  the  chill  of  intermittent  fever  and  often  in  exanthematous 
and  some  other  fevers,  so  that  we  cannot  consider  the  blood-pressure  and 
arterial  tension  as  having  any  such  definite  relation  to  fever  as  does  the 
pulse-rate. 

It  has  been  observed  by  Paschutin,  Senator,  and  Mendelson,"  that  the 
blood  pressure  rises  with  increasing  bodily  temperature,  produced  by  ex- 
posure to  heat.  Mendelson  found  that  the  pressure  begins  to  sink  as  the 
temperature  approaches  a  point  incompatible  with  life.  In  these  experiments 
the  animals  were  subjected  to  rapid  elevations  of  temperature.  I  find  that 
when  a  rabbit  is  gradually  and  cautiously  heated  in  the  hot  box  used  in  my 
experiments,  the  rise  of  temperature  is  less  marked,  and  may  not  surpass 
even  for  temperatures  of  107°  F.  (41.7°  C),  the  normal  limits  of  variation 
which  may  be  found  in  the  blood-pressure  of  the  same  animal  examined  at 
different  times.  These  measurements,  however,  are  not  very  conclusive, 
for,  as  has  been  already  remarked,  rabbits  which  have  been  operated  upon 
do  not  stand  well  artificial  heating. 

I  have  observed  that  the  rhythmical  contractions  of  the  bloodvessels  of  the 
rabbit's  ear  are  feeble  or  absent  when  the  temperature  is  much  elevated  by 

"Von  Basch,  Zadek,  Arnhelm,  Wetzel. 

*"  Paschutin:  Ludwig's  Arbeiten,  1873.  Senator:  DuBois-Reymond's  Archlv, 
1883,  Supplant-Band.  Mendelson:  On  the  Renal  Circulation  during  Fever,  Amer. 
Journ.  Medical  Sciences,  October,  1883. 


GENERAL  PATHOLOGY  OF  FEVER         339 

artificial  heating;  whereas,  it  will  be  remembered  that  in  experimental  septic 
fever  these  contractions  are  irregular  and  exaggerated. 

Upon  the  whole,  1  think  that  we  are  justified  in  concluding  that  the 
variations  of  arterial  tension  in  fevers  are  much  less  dependent  upon 
increased  temperature  than  upon  other  factors,  such  as  infection. 

But  the  corner-stone  of  the  doctrine  which  teaches  that  a  chief  source  of 
danger  in  fevers  is  the  elevation  of  temperature  is  not  the  effect  of  increased 
temperature  upon  the  pulse-rate  or  the  arterial  pressure,  but  it  is  the  belief 
that  prolonged  high  temperature  exerts  a  directly  paralyzing  influence  upon 
the  heart.  The  main  support  of  this  belief  is  not  the  admitted  fact  that 
extremely  high  temperatures  paralyze  the  heart,  for  these  critical  tem- 
peratures lie  far  above  the  ordinary  high  temperatures  of  fever,  and  in  a 
region  where  all  admit  the  dangers  of  the  excessive  internal  heat.  The 
stately  superstructure  has  been  built  up  chiefly  on  the  basis  of  experiments 
showing  that  when  the  internal  temperature  of  animals  has  been  main- 
tained for  some  time  at  a  high  point  by  exposure  to  external  heat,  paren- 
chymatous or  fatty  degeneration  of  the  heart  muscle  ensues.  It  is  true  that 
all  experiments  are  not  in  accord  upon  this  point,  and  that,  as  a  rule,  patho- 
logical anatomists  have  not  given  adherence  to  the  doctrine  that  parenchy- 
matous degenerations  are  chiefly  dependent  upon  high  temperature,  still 
this  doctrine  has  gained  a  wide  acceptance  among  clinical  men,  and  is  advo- 
cated with  especial  force  by  Liebermeister.  I  have  therefore,  thought  it 
desirable  in  my  experiments  to  give  especial  attention  to  this  question. 

Among  previous  experimenters  on  artificial  heating  of  animals,  Iwaschke- 
witsch,  Wickham  Legg,  and  Litten  may  be  mentioned  as  finding  parenchy- 
matous or  fatty  degeneration  of  the  heart,  liver,  and  kidneys ;  and  Walther, 
Obernier,  and  Naunyn  as  obtaining  only  negative  results. 

It  is  not  necessary  here  to  enter  into  a  criticism  of  these  different  experi- 
ments, which  are  of  very  unequal  value.  Litten's  "  experiments  on  the  one 
side,  and  Naunyn's  "  on  the  other,  appear  to  be  the  most  carefully  conducted. 
Litten,  whose  experiments  are  those  usually  cited,  kept  guinea-pigs  in  a 
double-walled  metallic  box  which  was  at  a  constant  temperature  of  98.8°  F. 
(37°  C.)  with  dry  air,  or  of  96.6°  F.  (36°  C.)  with  moist  air.  He  never 
failed  to  find  fatty  degeneration  at  the  end  of  thirty-six  to  forty-eight  hours. 
The  liver  was  first  affected,  and  then  the  heart  and  kidneys,  which  become 
fatty  by  the  second  or  third  day.  The  animals  did  not  survive  longer  than 
five  or  six  days,  and  by  that  time  the  fatty  degenerations  had  reached  an 
extreme  degree.    Von  Recklinghausen  "  urges  with  apparent  justice  against 

**  Litten:    Virchow's  Archiv,  Bd.  70. 
"Naunyn:   Op.  cit. 

*■'  Von  Recklinghausen :  Handb.  d.  Allg.  Pathologie  d.  Kreislause  u.  d.  Ernah- 
rung,  p.  512,  Stuttgart,  1883. 


340  CARTWRIGHT  LECTURES 

these  experiments  that  the  enforced  inactivity  of  the  muscles  and  the  imper- 
fect ventilation  may  have  had  as  much  to  do  in  causing  the  degenerations 
as  had  the  high  temperature.  These  objections  find  support  in  the  experi- 
ments of  Xaunyn,  who,  making  use  of  a  much  larger  and  better  ventilated 
heating  box  than  Litten  failed  to  find  any  parenchymatous  or  fatty  degener- 
ation in  his  rabbits  after  they  had  been  exposed  for  two  weeks  to  higher  tem- 
peratures than  Litten  employed. 

As  my  experiments  confirmed  in  other  respects  Naunyn's  results,  I  was 
quite  unprepared  to  find  that  my  rabbits,  after  a  variable  period  of  artificial 
heating  quite  constantly  presented  fatty  degeneration  of  the  heart,  liver, 
and  kidneys,  and  sometimes  of  the  diaphragmatic  and  intercostal  muscles. 
I  never  found  the  degeneration  at  so  early  a  period  as  did  Litten.  It  was 
not  until  the  rabbit  had  been  kept  for  at  least  a  week  with  an  average  rectal 
temperature  of  106°  F.  (41.1°  C.)  that  the  degeneration  was  noticed,  and 
then  only  in  moderate  degree.  The  higher  and  the  less  fluctuating  the 
internal  temperature,  the  more  certain  was  the  degeneration  to  appear.  I 
could  reckon  upon  obtaining  rabbits  with  well-marked  fatty  degeneration 
of  the  heart  by  keeping  them  for  ten  days  with  a  rectal  temperature  between 
107°  F.  (41.7°  C.)  and  108°  F.  (42.2°  C).  I  am  not  prepared  to  account 
for  the  discrepancy  in  this  respect  between  Naunyn's  and  my  experiments. 
The  box  used  was  larger  than  that  employed  by  him,  and  every  care  was 
taken  to  keep  it  well  ventilated  by  leaving  at  least  one-third  and  often  one- 
half  of  the  top  open. 

I  do  not  think  that  my  experiments  altogether  do  away  with  the  force  of 
von  Recklingliausen's  criticisms.  The  fact  that  in  these  experiments  the 
degeneration  made  its  appearance  at  the  end  of  a  week  or  ten  days,  and  in 
Litten's  in  forty-eight  hours,  to  say  nothing  of  Wickham  Legg  finding  it  at 
the  end  of  twelve  hours,  would  suggest  that  if  the  rabbits  were  heated  in  a 
still  larger  and  better  ventilated  apartment,  the  degeneration  might  not 
occur  at  all,  or  might  be  deferred  to  a  much  later  period.  In  my  opinion, 
however,  even  if  full  allowance  be  made  for  this  line  of  argument  we  must 
still  admit  that  prolonged  high  temperature  is  a  factor  in  the  causation  of 
fatty  degeneration. 

That  it  is  not  the  sole  factor  no  one  can  doubt.  As  is  well  known,  fatty 
degeneration  is  produced  by  anaemia  and  by  a  variety  of  poisons,  and  even 
in  fevers  most  pathologists  are  convinced  that  it  bears  a  closer  relation  to  the 
kind  and  degree  of  infection  than  it  does  to  the  height  of  the  temperature. 
It  is  more  frequently  absent  than  present  in  pneumonia,  even  where  there 
have  been  symptoms  of  heart  failure. 

The  kind  of  degeneration  present  in  my  rabbits  was  fatty  and  not  paren- 
chymatous.    Probably  all  who  make  many  post-mortem  examinations  will 


GENERAL  PATHOLOGY  OF  FEVER         341 

agree  with  von  Recklinghausen,  that  altogether  too  liberal  use  has  been 
made  of  the  diagnosis  of  parenchymatous  degeneration,  and  not  sufficient 
account  has  been  taken  of  the  anatomical  changes  of  the  parenchyma  pro- 
duced by  post-mortem  chemical  changes,  such  as  acid  formation,  etc. 

In  order  to  determine  what  influence  is  exerted  by  infection  combined 
with  high  temperature,  I  inoculated  a  rabbit  which  had  been  in  the  hot  box 
for  four  days,  with  the  bacilli  of  swine  plague.  These  bacilli,  if  not  identical 
with,  are  closely  allied  to  those  of  rabbit  septicaemia,  and  are  extremely 
virulent  for  rabbits.  In  thirty-six  hours  the  animal,  which  had  remained 
at  a  high  temperature  in  the  box,  was  dead,  with  characteristic  lesions  of  the 
disease,  and  the  most  extreme  fatty  degeneration  of  the  heart  and  other 
organs  was  found.  As  in  other  experiments  the  degeneration  had  not  made 
its  appearance  at  this  early  date,  there  can  be  no  doubt  that  the  infection 
was  an  important  element  in  the  causation.  That  it  received  powerful  sup- 
port in  the  high  temperature  however,  is  proven  by  the  fact  that  little  or  no 
degeneration  of  the  heart  is  observed  after  infection  with  this  organism 
when  the  animal  is  kept  at  ordinary  temperatures. 

Admitting,  then,  that  high  temperature  aids  in  the  causation  of  fatty 
degeneration  of  the  heart  in  fever,  the  question  arises.  What  do  we  know  of 
the  effects  of  this  degeneration  upon  the  functions  of  the  heart?  I  will  say 
nothing  of  the  growing  tendency  to  transfer  a  large  part  of  the  classical 
symptomatology  of  Quain's  fatty  heart  to  other  conditions,  particularly  to 
disease  of  the  coronary  arteries  and  chronic  myocarditis;  we  are  concerned 
at  present  only  with  the  occurrence  of  this  degeneration  in  fever.  Have  we 
not  been  somewhat  hasty  in  assigning  to  degeneration  of  the  heart's  muscle 
so  large  a  share  in  the  production  of  heart  failure  in  fevers?  One  cannot 
look  at  a  muscular  fibre  in  which  the  striated  substance  is  all  replaced  by 
fatty  globules,  and  suppose  that  its  functional  activity  was  unimpaired ;  but 
into  what  serious  errors  should  we  fall  if  we  attempted  to  deduce  from  the 
anatomical  changes  in  the  liver  cells  or  the  renal  epithelium  the  correspond- 
ing functional  disturbances  ?  Certain  it  is  that  symptoms  which  are  usually 
considered  those  of  heart  failure  are  often  enough  present  in  fevers  without 
finding  at  the  autopsy  any  degeneration  of  the  heart;  and,  on  the  other 
hand  such  degeneration  may  be  discovered  without  any  history  of  these 
symptoms,  although,  of  course,  the  two  are  often  associated. 

In  the  face  of  these  doubts  it  seemed  desirable  to  determine,  if  possible, 
experimentally  the  damage  inflicted  upon  the  cardiac  functions  by  the  pres- 
ence of  fatty  degeneration  of  the  heart  muscle.  That  this  degeneration  may 
exist  without  apparent  injury  is  rendered  probable  by  the  fact  that  a  rabbit 
which  has  been  kept  for  three  weeks  in  the  hot  box  at  a  high  temperature, 
and  in  which  there  is  every  reason  to  suppose  that  fatty  degeneration  has 


342  CAETWRIGHT  LECTURES 

oooiirred,  may  present  no  symptoms  of  heart  paralysis,  and  when  removed 
from  the  box  appear  and  remain  perfectly  normal.  An  instance  has  already 
been  mentioned  where  one  rabbit  at  the  end  of  three  weeks  was  killed  and 
presented  marked  fatty  degeneration  of  the  heart;  and  another,  which  had 
possessed  a  higher  average  rectal  temperature,  was  removed  from  the  box 
at  the  end  of  the  same  period,  and  appeared  for  ten  days  perefctly  normal, 
when  it  was  used  for  another  purpose.  That  this  degeneration  can  be  recov- 
ered from  is,  moreover,  rendered  probable  by  clinical  experience,  and  is 
universally  admitted. 

Once  in  teasing  out,  in  a  warm  room,  a  bit  of  fatty  heart  muscle  from  one 
of  the  rabbits,  I  made  a  curious  observation.  Near  the  edge  of  the  cover 
glass,  where  there  was  a  slight  current  in  the  physiological  salt  solution, 
rhythmical  contraction  was  observed  in  a  group  of  muscle-fibres.  This 
interesting  spectacle  could  be  watched  under  the  microscope  for  ten  minutes. 
These  contracting  fibres  were  filled  with  fatty  globules,  and  only  here  and 
there,  and  then  indistinctly,  could  any  trace  of  striation  be  detected.  This 
observation  teaches  that  a  fatty  degenerated  muscular  fibre  is  capable  of  con- 
traction, but,  of  course,  warrants  no  further  conclusions. 

Far  more  important  than  any  inferences  which  can  be  drawn  from  such 
observations  is  the  measurement  of  the  actual  blood-pressure  in  animals 
wliose  hearts  have  undergone  fatty  degeneration.  This  I  have  done  in  three 
instances.  The  rabbit  was  removed  from  the  box  at  the  end  of  ten  days  to 
two  weeks,  and  the  pressure  in  the  carotid  artery  was  measured  by  a  mercury 
manometer  attached  to  Ludwigs  kymograph.  In  no  instance  was  the  blood- 
pressure  found  to  be  lower  than  that  normally  present  in  rabbits.  In  an 
experiment  recently  ])crformed,  the  average  pressure  was  125  mm.  of  mer- 
cury; the  ])u]sations  were  regular;  the  heart  responded  to  stimulation  of  the 
vagi  in  an  entirely  normal  manner.  After  such  stimulation  the  pressure  in 
one  case  rose  to  ITO  mm.  of  mercury.  Immediately  after  the  measurement 
of  the  blood-pressure  the  rabbit,  as  in  the  previous  instances,  was  killed,  and 
marked  fatty  degeneration  of  the  muscular  fibres  was  found.  In  many  of 
tlic  fibres  the  striation  could  not  be  made  out,  and  only  fatty  globules  were 
visible;  in  others,  which  also  contained  fatty  granules,  the  striation  was  dis- 
tinct. The  degeneration  involved  the  whole  muscular  substance  of  the 
heart.  A  similar  appearance  in  a  human  heart  wouhl  be  considered  to  indi- 
cate well-marked  fatty  degeneration. 

These  experiments  show  that  a  rabbit's  heart  which  has  undergone  marked 
fatty  degeneration  from  exposure  to  heat,  may  perform  its  functions  to  all 
appearances,  and  for  the  time  being,  in  a  perfectly  normal  manner. 

There  is  at  least  one  consideration  which  should  make  us  cautious  in 
drawing  far-reaching  conclusions  from  these  experiments.     There  are  dis- 


GENERAL  PATHOLOGY  OF  FEVER         343 

eases  of  the  heart — I  need  only  refer  to  lesions  of  the  coronary  arteries — in 
which  the  functions  of  the  organ  are  performed  for  a  longer  or  shorter  time, 
apparently  in  a  perfectly  normal  way,  and  then  heart  failure  suddenly 
appears.  It  is  probable  that  here  too  the  blood  pressure  would  be  found 
normal  at  a  certain  period  of  the  disease,  and  still  it  would  be  an  error  to 
suppose  that  the  lesion  does  not  damage  the  heart. 

Whatever  force  there  may  be  in  this  analogy,  I  still  think  that  these 
experiments,  as  well  as  careful  pathological  and  clinical  observations,  neces- 
sitate some  revision  of  the  current  opinions  concerning  the  significance  of 
fatty  degeneration  of  the  heart  in  fever. 

So  much  time  has  been  devoted  to  a  consideration  of  the  effects  of  heat 
upon  the  respiration  and  the  heart  that  the  limits  of  the  present  lecture  will 
permit  hardly  more  than  a  summary  of  the  effects  exerted  by  heat  upon 
other  functions  and  organs  of  the  body.  On  account  of  the  great  clinical 
importance  of  the  subject  it  seemed  desirable  to  treat  with  especial  fulness 
the  influence  of  increased  temperature  on  the  heart. 

What  part  has  increased  temperature  in  producing  febrile  consumption 
of  tissue  ?  In  the  first  lecture  mention  was  made  of  Pfliiger's  experiments 
showing  that  animals  with  elevated  temperature,  produced  by  exposure  to 
heat,  absorb  more  oxygen  and  excrete  more  carbonic  acid  than  at  the  normal 
temperature.  This  is  in  conformity  with  the  general  law  that  within  certain 
limits  cell  activity  is  more  energetic  at  high  than  at  low  temperatures.  It 
was  also  shown  in  the  first  lecture  that  only  a  comparatively  small  part  of  the 
increased  oxygen  absorption  and  carbonic  acid  elimination  in  fever  can  be 
referred  to  the  immediate  effects  of  high  temperature.  It  has  not  been 
demonstrated  that  the  respiratory  gases  in  human  beings  are  increased  by 
artificial  elevation  of  temperature.  Indeed  Voit**  was  unable  to  find  any 
such  effect  of  increased  temperature  in  human  beings  on  the  respiratory 
gases  as  both  he  and  Pfliiger  observed  in  animals. 

Inasmuch  as  increased  disintegration  of  nitrogenous  material  is  such  a 
prominent  disorder  in  fever,  much  attention  has  naturally  been  given  to 
determining  how  far  this  can  be  explained  by  elevated  temperature.  That 
it  cannot  all  be  so  explained  is  proven  by  the  interesting  observation  of 
Sydney  Ringer,  that  excessive  elimination  of  urea  antedates  the  rise  of 
temperature  in  intermittent  fever,  and  Xaunyn  has  found  the  same  to  be 
true  of  the  septic  fever  of  dogs.  The  experiments  which  have  been  made 
to  determine  the  influence  of  artificial  heating  on  the  amount  of  urea 
excreted  by  man  and  by  animals  have  yielded  contradictory  results.  A  num- 
ber of  these  experiments  are  of  little  or  no  value,  because  no  attention  was 

♦'Voit:    Zeitschrift  fiir  Biologie,  Bd.  XIV. 


344  CARTWRIGHT  LECTURES 

given  to  establishing  beforehand  nitrogen  equilibrium.  Schleich's*'  ex- 
periments may  be  mentioned  as,  perhaps,  the  most  accurate  of  those  show- 
ing an  increase  in  the  urea  excreted  under  the  influence  of  exposure  to  heat. 
The  more  recent  experiments  of  Simanowsky  "  were  made  in  Voit's  labora- 
tory upon  a  dog  with  especial  precautions  as  to  the  establishment  of  nitro- 
gen equilibrium.  He  failed  to  find  any  increase  in  the  excretion  of  urea 
as  the  result  of  exposure  to  external  heat.  While  then  this  question  must 
be  left  at  present  sub  judice,  there  can  be  no  doubt  that  only  a  part  at  least 
of  the  excessive  disintegration  of  nitrogenous  substance  in  fever  can  be 
assigned  to  the  influence  of  the  increased  temperature. 

The  loss  of  weight  exhibited  by  animals  kept  for  a  long  time  in  a  hot 
atmosphere  is  usually  explained  by  the  excessive  evaporation  of  water  from 
the  body.  In  many  of  my  experiments  the  rabbits  were  freely  supplied  with 
food  and  water,  and  still  the  loss  of  weight  was  very  noticeable.  I  am 
inclined,  therefore,  to  attribute  to  the  increased  temperature  under  these 
conditions  a  decided  influence  upon  the  consumption  of  tissue. 

Senator  "  found  the  urine  of  rabbits  artificially  heated  to  contain  more 
albumen  than  is  ever  found  in  the  urine  of  healthy  rabbits.  This  observation 
I  have  not  been  able  to  confirm  on  the  rabbits  in  my  experiments  and  prob- 
ably this  difference  is  to  be  explained  by  the  more  rapid  and  intense  heating 
employed  in  Senator's  experiments.  Senator  explains  the  heat  albuminuria 
by  the  rise  of  arterial  pressure  in  the  renal  vessels,  but  this  is  not  in  con- 
formity with  the  interesting  experiments  of  Mendelson,"  who  found  by 
means  of  Roy's  oncometer  that  both  in  thermic  and  in  septic  fevers  of  dogs 
the  kidney  is  anaemic,  while  the  general  blood-pressure  is  elevated. 

No  satisfactory  explanation  has  yet  been  offered  of  the  diminution  of 
perspiration  which  distinguishes  fever  so  strikingly  from  the  condition  pro- 
duced by  exposure  to  high  external  temperatures.  Luchsinger's  assertion 
that  this  is  the  result  of  lessened  irritability  of  the  sweat  centres  in  the 
spinal  cord  remains  to  be  proven,  and  at  the  best  is  not  a  satisfying 
explanation. 

Bokai,"  in  a  recent  experimental  research  on  intestinal  peristalsis  in 
thermic  and  in  septic  fevers,  comes  to  the  conclusion  that  the  constipation 
of  fever  is  to  be  explained  by  the  heated  blood  stimulating  the  nerves  inhibit- 
ing intestinal  peristalsis.  If  this  should  be  confirmed,  then  it  would  be 
proven  that  at  least  three  symptoms  of  fever,  the  quickened  respiration  and 
pulse  and  the  constipation  are  direct  effects  of  elevated  temperature. 

"  Schleich:    Arch.  f.  exp.  Path.  u.  Pharm.,  Bd.  IV. 

"Simanowsky:    Zeitschr.  f.  Biologie,  Bd.  XXI. 

"Senator:    DuBois-Roymond's  Archiv,  1883,  Supplement-Band,  • 

*' Mendelson :    Op.  cit. 

♦»  Bokai:   Archiv  f.  exp.  Path.  u.  Pharm.,  Bd.  23. 


GENERAL  PATHOLOGY  OF  FEVER         345 

When  we  consider  the  important  nutritive  changes  in  the  muscles  accom- 
panying increased  thermogenesis,  we  shall  be  inclined  to  attribute  in  part, 
at  least,  to  these  alterations  and  the  associated  abnormal  innervation,  rather 
than  to  increased  temperature,  the  muscular  pains  and  weakness  which  form 
such  an  early  and  frequent  complaint  in  many  fevers. 

The  investigations  hitherto  published  of  changes  in  the  blood  produced  by 
increased  temperature  within  febrile  limits  are  not  of  sufficiently  definite 
and  satisfactory  nature  to  warrant  any  consideration  on  the  present  occasion. 

Nor  am  I  acquainted  with  any  experimental  evidence  (save  Bokai's  work 
already  mentioned)  that  increased  temperature  is  concerned  in  the  produc- 
tion of  the  digestive  disorders  of  fever.  It  has  already  been  said  that  the 
rabbits  with  high  internal  temperatures  in  the  hot  box  ate  greedily,  but  these 
voracious  animals  cannot  be  considered  favorable  subjects  to  test  this 
question. 

Especial  emphasis  has  been  laid  by  Liebermeister  and  those  who  accept 
his  teachings  upon  the  dependence  of  the  nervous  symptoms  of  fever,  par- 
ticularly the  so-called  typhoid  symptoms,  on  the  elevation  of  temperature. 
There  is,  however,  abundant  clinical  evidence  to  disprove  this  doctrine. 
Reference  need  be  made  only  to  relapsing  fever,  and  especially  to  the  aseptic 
fever  described  by  Genzmer  and  Volkmann,  in  which  there  is  entire  absence 
of  the  whole  group  of  so-called  nervous  symptoms.  Moreover,  Lieber- 
meister's  opinion  in  this  respect  is  not  supported  by  adequate  experimental 
evidence.  Unless  the  temperature  of  the  brain  or  of  the  entire  animal  be 
brusquely  raised  to  a  high  point  by  coarse  methods,  no  disturbance  of  the 
cerebral  functions  is  noticed  until  the  temperature  reaches  a  critical  point, 
beyond  which  further  increase  is  likely  to  prove  rapidly  fatal.  At  this 
critical  point  the  animal,  which  before  has  lain  quietly,  becomes  very  uneasy, 
and  if  the  temperature  rise  higher  it  has  convulsions  and  coma  and  dies. 

I  have  endeavored  to  bring  before  you  in  this  lecture  the  experimental  evi- 
dence relating  to  the  effects  of  increased  temperature  upon  the  general  con- 
dition of  the  body  and  upon  the  functions  of  its  various  organs.  I  have 
given  account,  as  briefly  as  possible  of  some  experiments  which  perhaps  shed 
additional  light  upon  this  important  subject.  In  the  course  of  this  lecture 
emphasis  has  repeatedly  been  laid  upon  the  necessity  of  controlling  the 
results  of  the  experimental  method  by  clinical  observation,  and  here  and 
there  I  have  endeavored  to  institute  this  control.  Further  than  this  I  shall 
not  attempt  to  set  before  you  the  clinical  evidence  regarding  the  effects  of 
increased  temperature  in  fever.  There  are  those  here  more  competent  than 
I  to  deal  with  this  side  of  the  question.  We  may  feel  assured  that  when  all 
the  facts  are  before  us  and  are  properly  interpreted,  there  can  be  no  lack  of 
harmony  between  the  results  of  experimental  and  those  of  clinical  investi- 
gations. 
25 


346  CAETWRIGHT  LECTURES 

Lecture  III 

THE  ETIOLOGY  OF  FEVER 

We  considered  in  the  last  lecture  the  experimental  evidence  concerning 
the  effects  of  increased  bodily  temperature.  An  advantage  of  the  experi- 
mental over  the  clinical  method  of  investigating  this  subject  is  that  it  enables 
us  to  study  the  effects  of  heat  upon  the  whole  body  and  its  various  functions 
without  the  intervention  of  disturbing  factors,  such  as  infection,  which 
complicate  the  clinical  analysis  of  febrile  phenomena  with  reference  to  this 
question. 

We  found  that  animals  may  be  kept  at  high  febrile  temperatures  for  at 
least  three  weeks  without  manifesting  any  serious  symptoms.  The  only 
functional  disturbances  which  could  be  attributed  directly  to  the  influence 
of  the  elevated  temperature  were  increased  frequency  of  respiration  and 
quickened  pulse.  The  rapid  respiration  was  found  to  be  due  partly  to  stimu- 
lation of  the  skin  by  external  heat  and  by  the  warmed  blood,  and  partly  to 
the  action  of  the  warmed  blood  on  the  respiratory  centres.  The  quickened 
pulse  could  be  positively  referred  to  the  effect  of  the  warmer  blood  upon  the 
heart  itself.  No  definite  relation  could  be  established  between  the  varia- 
tions of  arterial  tension  which  occur  in  fever  and  the  height  of  the  tempera- 
ture. 

Although  the  experiments  narrated  showed  that  prolonged  high  tempera- 
ture is  an  element  in  the  causation  of  fatty  degeneration  of  the  heart,  they 
also  indicated  that  other  factors,  such  as  infection,  are  concerned  in  the 
production  of  this  lesion.  Moreover,  experimental  evidence  was  found  in 
support  of  clinical  facts  showing  that  this  alteration  may  exist  without 
serious  interference  with  the  functions  of  the  heart,  so  that  the  conclusion 
seems  justified  that  failure  of  the  heart's  power  in  fever  is  less  an  effect  of 
high  temperature  than  of  other  concomitant  conditions. 

Of  the  other  disturbances  in  fever  we  learned  that  the  increased  con- 
sumption of  tissue  can  be  explained  only  in  relatively  small  part  by  the 
elevation  of  temperature.  The  lessened  perspiration,  the  renal  disorders, 
and  the  digestive  disturbances  (with  the  possible  exception  of  constipation) 
are  referable  also  chiefly  to  other  causes  than  the  increased  temperature. 
Both  experimental  and  clinical  observations  strongly  support  the  view  now 
widely  accepted  that  the  disturbances  of  the  sensorium  which  constitute  so 
prominent  a  part  of  the  group  of  so-called  typhoid  symptoms,  are  dependent 
in  far  higher  degree  upon  infection  or  intoxication  than  upon  the  heightened 
temperature. 

Although  no  attempt  was  made  to  analyze  in  detail  the  clinical  evidence 
relating  to  the  effects  of  liigh  temperature,  attention  was  called  to  the  fact 


GENERAL  PATHOLOGY  OF  FEVER         347 

that  the  absence  of  all  serious  symptoms  in  many  cases  of  relapsing  fever, 
and  in  the  so-called  aseptic  fevers  in  spite  of  prolonged  high  temperatures, 
strongly  support  the  conclusions  derived  from  the  experimental  study  of  the 
effects  of  heat  upon  man  and  animals.  Even  in  fevers,  such  as  typhoid  fever 
and  pneumonia,  where  the  height  of  the  temperature  is  undoubtedly  a  most 
important  index  of  the  severity  of  the  disease,  there  exists  no  such  parallelism 
between  the  temperature  and  the  nature  and  the  severity  of  the  other  symp- 
toms as  we  should  expect  if  these  symptoms  were  caused  by  the  increased 
heat  of  the  body. 

It  was  emphasized  that  the  results  of  experimental  investigations  should 
not  be  permitted  to  control  the  treatment  of  fevers,  more  particularly  the 
use  of  so-called  antipyretic  agents.  These  agents,  whether  hydrotherapeutic 
or  medicinal,  influence,  as  is  well  known,  many  functions  besides  reducing 
the  temperature.  I  need  only  refer  to  the  powerful  influence  of  cold  baths 
upon  the  circulation  and  the  nervous  system,  and  to  the  action  of  antipyrin 
and  other  antithermic  drugs  upon  the  nervous  system. 

Reasons  were  given  for  assigning  to  hyperpyrexia  and  insolation  a  position 
separate  from  other  febrile  conditions  in  the  discussion  as  to  the  effects  of 
elevated  temperature. 

Before  leaving  this  subject  of  the  effects  of  increased  temperature,  I  wish 
to  call  attention  to  one  consideration  which  should  perhaps  influence  our 
opinion  on  this  much  disputed  question.  Is  it  a  matter  of  indifference,  so 
far  as  the  effects  of  febrile  temperatures  are  concerned,  in  what  manner  the 
increase  of  temperature  is  brought  about?  We  have  seen  that  heat  regula- 
tion, heat  production,  and  heat  loss  are  disturbed  in  fever ;  but,  as  experience 
shows,  not  always  in  the  same  manner  or  the  same  degree.  In  one  case  the 
incoordination  of  the  regulating  mechanism  may  be  most  apparent,  the 
temperature  fluctuating  strangely  up  and  down;  in  another  case  the  heat- 
producing  processes  are  excited  to  the  utmost ;  and  in  another  the  circulatory 
changes  in  the  skin,  the  vasomotor  disturbances,  are  the  most  prominent 
phenomena.  Now  this  varying  interplay  of  the  factors  which  cause  febrile 
rise  of  temperature  doubtless  corresponds  to  varying  conditions  of  innerva- 
tion, of  structure  and  of  function  of  certain  tissues  of  the  body.  May  we  not 
reasonably  suppose  that  these  varying  conditions  of  the  tissues  directly 
associated  with  the  rise  of  temperature  may  influence  their  tolerance  of 
increased  body  heat?  We  have  not  the  experimental  or  the  clinical  data 
which  would  enable  us  to  give  a  definite  answer  to  the  question  here  pro- 
pounded, and  it  would  lead  me  too  far  from  the  theme  of  the  present 
lecture  to  attempt  to  sift  the  equivocal  evidence  which  might  be  gathered. 
I  suggest  this  question,  however,  as  one  worthy  of  more  attention  than  it 
has  hitherto  received. 


348  CARTWRICtHT  LECTURES 

I  wish  now  to  invite  your  attention  to  some  considerations  concerning  the 
etiology  of  fever.  In  this  era,  when  etiological  studies  occupy  the  foremost 
rank  in  medical  science,  it  will  naturally  be  expected  that  a  discussion  of 
tlie  general  pathology  of  fever,  even  though  it  does  not  aim  at  completeness, 
will  not  leave  wholly  untouched  the  etiological  aspect  of  the  subject. 

The  general  etiology  of  fever  relates  mainly  to  a  consideration  of  the 
agents  producing  fever,  the  so-called  pyrogenic  substances.  It  is,  moreover, 
only  certain  general  characters  of  these  agents  which  can  be  properly  con- 
sidered here.  Most  of  the  questions  which  at  present  engage  so  prominently 
the  attention  of  physicians  concerning  the  specific  causes  of  individual 
fevers  belong,  of  course,  to  the  special  etiology  of  fevers,  and  therefore  do 
not  lie  within  the  limits  of  our  subject.  But  even  with  these  limitations  we 
cannot  in  treating  of  the  general  etiology  of  fever  consider  the  febrile  proc- 
esses so  much  in  the  abstract  as  we  have  done  hitherto.  We  must  come  into 
closer  contact  with  the  individual  forms  of  fever. 

At  the  start  it  should  be  said  that  probably  in  no  instance  are  we  ac- 
quainted with  the  actual  substance  or  substances  upon  which  the  febrile  dis- 
order of  animal  heat  immediately  and  directly  depends.  We  deal  here,  as 
elsewhere  in  medicine,  not  with  direct  but  with  remote  causes.  But  in  no 
department  of  etiology  have  we  advanced  nearer  the  proximate  causes  than 
in  many  of  the  infectious  fevers.  To  be  convinced  of  the  immense  progress 
which  has  been  brought  about  by  the  etiological  study  of  fevers,  let  one  glance 
over  some  of  tlie  older  books  on  fevers,  such  as  Percy's  or  Selle's,"  with  their 
endless  divisions  into  symptomatic  genera  and  species,  and  their  barren 
speculations.  Percy,  for  instance,  describes  no  less  than  one  hundred  and 
fifteen  different  kinds  of  fever. 

In  all  ages  it  has  been  customary  to  divide  fevers  into  two  great  groups, 
viz. :  those  which  are  secondary  to  some  local  cause,  usually  an  inflammation, 
and  those  which  cannot  be  explained  by  the  presence  of  any  local  lesion.  The 
explanation  of  the  s}Tnptomatic  seemed  so  much  clearer  than  that  of  the 
essential  fevers  that  attempts  have  repeatedly  been  made  to  place  all  fevers 
in  the  symptomatic  group.  It  is  a  curious  fact  that  the  two  methods  which 
have  been  of  the  greatest  service  in  the  study  of  fevers,  each,  when  first 
introduced,  led  to  an  entire  misconception  of  the  nature  of  fever.  Boerhaave, 
who  was  the  first  to  make  any  extensive  use  of  the  thermometer  at  the  bed- 
side, supposed  that  this  instrument  indicated  a  reduction  of  the  bodily  tem- 
perature during  the  febrile  chill.  He  therefore  taught  that  increased  fre- 
quency of  the  pulse  and  not  the  elevation  of  temperature  is  the  constant  and 
essential  symptom  of  fever.    If  we  except  de  Haen's  correction,  which  never 

'"Percy:  Die  gesammte  Fleberlehre,  Pesth,  1820.     The  original  is  in  French. 
Selle:    Rudimenta  Pyretologiae  Methodicae,  Berolini,  1773. 


GENERAL  PATHOLOGY  OF  FEVER         349 

became  widely  known,  it  was  not  until  the  middle  of  the  present  century 
that  Boerhaave's  error  was  overthrown.  A  no  less  serious  misconception 
sprang  from  the  study  of  the  pathological  anatomy  of  fevers  in  France  dur- 
ing the  early  part  of  the  present  century.  The  exaggerated  ideas  of  the 
immediate  followers  of  Bichat  as  to  what  can  be  accomplished  by  pathological 
anatomy  led  them  to  the  belief,  for  a  long  time  widely  accepted,  that  there 
is  no  such  thing  as  an  essential  fever,  that  all  fevers  are  symptomatic  of  some 
local  disease.  This  error  of  Broussais,  one  of  the  most  influential  and  elo- 
quent medical  teachers  of  this  century,  is  plainly  traceable  partly  to  the  fact 
that  his  autopsies  were  chiefly  of  typhoid  fever,  and  partly  to  the  belief  that 
the  lesions  found  at  the  autopsy  suffice  to  explain  all  of  the  manifestations 
of  the  disease  during  life.  But  we  need  not  stop  to  trace  the  fate  of  the 
various  attempts  to  overthrow  the  doctrine  of  essential  fevers.  I  have  men- 
tioned one  attempt  chiefly  on  account  of  the  suggestive  lessons  it  conveys 
rather  than  from  a  desire  to  enter  into  historical  details  which  I  have  hitherto 
purposely  avoided. 

The  division  of  fevers  into  symptomatic  and  essential  fevers  is  one  of  un- 
doubted practical  utility,  and  is  not  likely  to  be  abandoned.  But  it  cannot 
truthfully  be  said  that  this  popular  classification  has  been  of  much  assist- 
ance in  advancing  our  knowledge.  Close  inspection  shows  that  the  boundary 
lines  between  the  two  groups  of  fevers  are  vague  and  shadowy.  Probably  no 
one  any  longer  believes  that  traumatic  fever,  the  principal  type  of  the 
symptomatic  group,  is  due  to  increased  production  of  heat  in  the  seat  of 
inflammation,  which,  acting  Hke  a  furnace,  was  once  thought  to  warm  the 
whole  organism,  or  to  the  irritation  of  nerves  connected  with  the  inflamed 
region.  The  opinion  of  Billroth  and  of  Weber  is  now  generally  accepted, 
that  traumatic  fevers  are  caused  by  the  absorption  of  pyrogenic  substances 
from  the  inflamed  district.  Symptomatic  fevers  as  well  as  essential  fevers, 
therefore,  are  dependent  upon  the  presence  within  the  blood  of  fever-produc- 
ing agents.  Many  essential  fevers,  moreover,  resemble  the  symptomatic  ones 
in  the  existence  of  inflammation,  or  necrosis  at  the  portal  where  there  is 
reason  to  believe  that  the  pyrogenic  agents  gain  access  to  the  general  circu- 
lation. A  distinction  in  these  eases  cannot  be  based  on  the  ground  that  in 
symptomatic  fevers  only  chemical  substances,  although  possibly  the  products 
of  bacteria,  enter  the  circulation,  and  in  essential  fevers  microorganisms 
invade  the  blood,  for  such  a  distinction  woidd  place  cholera  and  possibly 
tetanus  and  typhoid  fever  among  the  symptomatic  fevers.  These  considera- 
tions show  how  vague  and  unsatisfactory  are  the  distinctions  between  symp- 
tomatic and  essential  fevers.  Still,  similar  criticisms  can  be  made  of  many 
of  our  artificial  classifications  which  nature  is  under  no  compact  to  observe, 
and  we  should  undoubtedly  be  put  to  great  inconvenience  if  we  attempted  to 


350  CAETWRIGHT  LECTURES 

dispense  with  the  epithets  symptomatic  and  essential  as  applicable  to  differ- 
ent forms  of  fever.  Tliere  are,  however,  other  points  of  view  which  seem  to 
me  more  fruitful  in  the  study  of  the  etiology  of  fever  than  those  embodied 
in  these  distinctions.  I  refer  to  the  differences  in  the  nature  of  fever-pro- 
ducing agents,  concerning  which  our  knowledge,  although  still  very  imper- 
fect, has  been  materially  increased  within  recent  years.  And  here  agam  we 
are  greatly  indebted  to  the  results  of  experiments  upon  animals. 

Much  light  has  been  shed  upon  the  causes  of  a  certain  class  of  fevers  by  a 
series  of  experiments,  which  received  their  impulse  from  the  important 
studies  of  Alexander  Schmidt  and  his  pupils  upon  the  physiology  of  the 
blood.  A  particular  direction  was  given  to  these  experiments  by  the  often 
repeated  observation  that  fever  and  other  injurious  effects  may  follow  the 
transfusion  of  blood,  especially  when  the  blood  of  one  species  of  animal  is 
transfused  into  an  animal  of  another  species.  In  order  to  test  the  supposi- 
tion that  these  bad  symptoms  are  due  to  an  excess  of  fibrin  ferment  Kohler  " 
injected  into  the  vessels  of  animals  blood  made  rich  in  fibrin  ferment  and 
fibrino-plastic  substance,  and  found  that  this  blood  when  injected  in  large 
amount  into  the  jugular  vein  causes  sudden  death  by  rapid  coagulation  of 
the  blood  in  the  right  heart  and  pulmonary  arteries,  but  when  injected  in 
smaller  amount  or  in  a  different  manner  produces  a  typical  febrile  attack 
bearing  a  close  resemblance  to  that  following  the  injection  of  putrid  fluids. 
Angerer"  then  found  that  a  similar  fever,  although  less  intense  and  more 
gradual  in  its  development,  may  be  produced  by  the  injection  of  blood  into 
the  peritoneal  cavity  or  the  subcutaneous  tissue,  or  even  by  an  extravasation 
of  blood.  Although  in  these  experiments  it  was  believed  that  fibrin  ferment 
is  the  pyrogenic  agent,  Edelberg"  was  the  first  to  produce  fever  and  other 
symptoms  of  intoxication  by  the  injection  of  this  ferment  isolated  according 
to  Schmidt's  method. 

In  the  light  of  these  experiments  it  was  to  be  expected  tliat  other  ferments 
would  be  examined  with  reference  to  their  pyrogenic  power.  Schmiede- 
berg"  discovered  that  injections  of  histozyme  into  the  blood  of  dogs  pro- 
duced high  fever  associated  with  general  illness,  and  particularly  with 
diarrhoea.  The  ferment  to  which  Schmiedeberg  has  given  the  name  histo- 
zyme he  believes  to  be  present  normally  in  small  amount  in  the  body,  and  to 
be  concerned  in  the  dissociation  of  the  nitrogenous  constituents  of  the  tissues. 
He  concludes  from  his  experiments  that  an  excessive  accumulation  in  the 

"  Kohler:   Ueber  Thrombose  und  Transfusion,  u.  s.  w.  Inaug.  Diss.,  Dorpat,  1877. 
"Angerer:     Klin.   u.   Exp.   Untersuch.   iib.   d.   Resorption   v.   Blutextravasate, 
Wurzburg.  1879. 

"  Edelberg:    Arch.  f.  exp.  Path.  u.  Pharm.,  Bd.  XII. 
"Schmiedeberg:   /bid.,  Bd.  XIV. 


GENERAL  PATHOLOGY  OF  FEVER         351 

body  of  this  normal  ferment  gives  rise  to  fever  with  increased  metamorphosis 
of  nitrogenous  materials.  Schmiedeberg  thinks  it  probable  that  the  fibrin- 
ferment  solutions  employed  by  Edelberg  in  his  experiments  contained  also 
histozyme,  and  that  the  pyrexia  was  due  to  the  latter  substance. 

Following  these  observations  concerning  the  pyrogenic  power  of  fibrin- 
ferment  and  histozyme  comes  the  discovery  of  von  Bergmann  and  Angerer  ^ 
that  injection  of  pepsin  and  of  trypsin  into  the  blood  of  dogs  causes  a  well- 
marked  fever  with  characters  like  those  of  the  other  ferment  intoxications 
described.  A  valuable  calorimetrical  study  of  pepsin  and  trysin  fevers  has 
been  made  by  "Wood,  Reichert,  and  Hare.°*  These  authors,  as  well  as  Ott," 
have  demonstrated  that  it  is  not  the  pepsin  and  the  trypsin  ferments  them- 
selves which  constitute  the  pyrogenic  agents,  but  some  contaminating  sub- 
stance, which  seems  to  be  a  peptone.  That  peptones  artificially  prepared 
contain  poisonous  principles  has  been  known  for  some  time,  and  Brieger  '^ 
has  succeeded  in  isolating  a  crystallizable  poisonous  ptomaine,  called  pepto- 
toxin,  from  commercial  peptone  and  from  that  formed  by  the  artificial  diges- 
tion of  fibrin.  This  ptomaine,  however,  is  not  identical  with  the  pyrogenic 
agent  found  by  Ott  and  by  Wood  and  his  colleagues  in  commercial  pepsin. 
To  this  list  of  pyrogenic  substances  obtained  from  impure  ferments  may  be 
added  leucin,  and,  according  to  Ott,  papayotin  and  neurin  which  produce 
marked  fever  when  injected  into  the  blood  in  small  quantity.  The  substance 
sold  under  the  name  of  papoid  possesses  marked  pyrogenic  power  when  its 
filtered  aqueous  solution  is  injected  into  the  blood.  This  substance  contains 
principles  belonging  to  the  peptone  or  albumose  group.  Dr.  Mall,  Fellow 
in  Pathology  at  the  Johns  Hopkins  University,  has  isolated  from  commercial 
papoid  a  bacillus,  which  in  pure  cultures  exerts  a  powerful  peptonizing 
action  on  fibrin  and  on  connective  and  elastic  tissues.  The  bacillus  itself 
is  not  pathogenic,  but  an  albumose  or  some  similar  substance  produced  by 
its  activity,  has  pyrogenic  power  when  injected  into  the  blood. 

It  does  not  appear  that  any  one  has  actually  isolated  the  pyrexial  agent 
from  the  various  ferments  employed  in  these  experiments.  Certainly  no  such 
agent  has  been  obtained  in  a  crystalline  form,  which  is  the  test  of  its  purity, 
if  we  except  Brieger's  pepto-toxin,  the  pyrogenic  capacity  of  which  has  not 
been  established.  It  has  been  alleged  tliat  the  fever-producing  agent  is  the 
same  in  all  these  ferment  intoxications,  but  this  has  not  been  proven  nor 
does  it  seem  probable. 

=^Von  Bergmann  u.  Angerer:     D.  Verhaltniss  d.  Fermentintoxication.     Fest- 
schrift:   Wiirzburger  Universitat,  1882,  I,  135. 
^Wood,  Reichert,  and  Hare:    Therapeutic  Gazette,  1886. 
"Ott:    Journal  of  Physiology,  VIII. 
"Brieger:    Ueber  Ptomaine,  Berlin,  1885. 


352  CARTWRIGHT  LECTURES 

On  better  grounds  it  has  been  urged  by  von  Bergmann  and  Angerer,  that 
all  of  the  substances  in  the  group  of  pyrexial  agents  now  under  consideration, 
cause  fever  by  producing  the  same  change  in  the  blood.  These  authors  claim 
that  this  change  is  the  formation  in  the  circulating  blood  of  an  excessive 
amount  of  fibrin  ferment,  which  leads  either  to  coagulation  or  to  stasis  in 
the  capillaries,  particularly  those  of  the  lungs  and  of  the  intestines.  One 
of  the  main  arguments  for  this  view  is  the  fall  of  blood  pressure  which  von 
Bergmann  and  Angerer  observed  after  injections  of  pepsin  and  of  pancreatin, 
but  this  fall  can  be  explained  in  other  ways  than  by  supposing  that  the 
pulmonary  capillaries  are  occluded,  and,  moreover.  Wood,  Reichert,  and 
Hare  find  that  the  blood  pressure  often  rises  in  the  course  of  pepsin  fever. 
It  does  not  seem  to  me  that  we  are  any  more  able  to  explain  in  exactly  what 
manner  the  pyrogenic  substances  act  in  this  class  of  fevers  than  in  other 
fevers.  The  idea,  however,  that  the  liberation  of  fibrin  ferment  in  abnormal 
quantity  is  capable  of  causing  fever,  finds  support  not  only  in  experiments 
which  have  been  mentioned,  but  also  in  the  fact  that  injections  of  haemo- 
globin solutions,  and  of  large  quantities  of  water  into  the  blood,  produce 
fever. 

But  you,  perhaps,  by  this  time  have  asked  yourselves  what  bearing  all  of 
these  experiments  with  various  pyrogenic  substances  have  upon  the  etiology 
of  human  fevers.  They  have,  in  my  judgment,  an  important  bearing  on  this 
subject.  However,  obscure  may  be  the  explanation  of  the  mode  of  action  of 
these  substances,  however  doubtful  may  be  their  exact  chemical  composition, 
they  have  certain  common  characteristics  which  are  calculated  to  shed  light 
upon  the  causation  of  some  obscure  febrile  disorders  of  human  beings.  In 
the  first  place,  the  members  of  this  group  of  pyrogenic  substances,  if  not 
identical  with  certain  physiological  ferments,  are  readily  produced  by  them, 
quite  independently  of  the  action  of  bacteria  or  other  microorganisms.  In 
the  second  place,  some  of  these  substances  are  present  normally  in  small 
amount  in  the  body,  and  if  their  elimination  is  impeded,  or  their  formation 
is  excessive,  there  is  reason  to  believe  that  they  become  efficient  causes  of 
fever.  In  the  third  place,  these  pyrogenic  substances  may  be  produced,  again 
without  the  action  of  bacteria,  in  extravasated  blood,  or  by  the  abnormal  dis- 
integration of  tissues,  and  if  they  are  absorbed  from  these  sources  in  such  a 
condition,  or  in  so  large  an  amount  that  nature  cannot  render  them  harmless, 
they  are  capable  of  producing  fever.  It  is  customary  to  call  the  morbid  condi- 
tion produced  by  the  absorption  of  these  sul)stances,  ferment  intoxication  in 
analogy  with  the  term  putrid  intoxication,  applied  to  the  diseases  caused  by 
the  absorption  of  the  products  of  putrefactive  bacteria.  The  term  ferment 
intoxication  seems  to  me  to  imply  more  than  our  knowledge  warrants,  but  it 
is  not  of  much  use  to  contend  against  names  which  have  gained  currency. 


GENERAL  PATHOLOGY  OF  FEVER         353 

It  is  probable  that  some  of  the  pyrogenic  agents  in  this  group  belong  to  the 
class  of  leucomaines,  but  our  present  information  regarding  these  bodies 
does  not  justify  any  positive  statement  on  this  point. 

Although  the  etiology  of  individual  fevers,  does  not  belong  to  our  subject, 
I  cannot  forbear  calling  your  attention  to  certain  febrile  conditions  which 
seem  to  be  produced  by  the  accumulation  of  substances  that  are  either  normal 
constituents  of  the  body  or  are  the  result  of  chemical  processes,  differing 
but  little  from  physiological  ones. 

To  this  category  probably  belongs  the-  so-called  aseptic  fever,  first  de- 
scribed by  Genzmer  and  Volkmann."^  These  surgeons  have  established  the 
fact  that  there  are  traumatic  fevers  not  caused  by  the  absorption  of  septic 
material,  and  that  severe  injuries  and  wounds  which  pursue  an  entirely 
aseptic  course,  are  not  infrequently  associated  with  considerable  elevation 
of  temperature.  This  aseptic  fever  is  usually  to  be  observed  with  extensive 
wounds  or  injuries  in  which  there  is  much  lacerated  tissue  or  extravasated 
blood  to  be  disintegrated  and  absorbed.  It  occurs  not  only  with  wounds 
correctly  treated  by  antiseptic  methods,  but  also  with  subcutaneous  injuries, 
particularly  fractures  of  the  large  bones,  where  there  can  be  no  suspicion 
of  the  action  of  bacteria.  Aseptic  traumatic  fever  differs  by  such  marked 
characteristics  from  septic  fever,  that  there  can  be  no  doubt  that  the  two 
types  of  fever  are  etiologically  distinct.  Aseptic  fever  has  no  prognostic 
significance;  its  only  symptoms  are  the  elevation  of  the  temperature,  which 
may  mount  to  104°  (40°  C),  or  even  105.8°  (41°  C),  and  the  increased 
frequency  of  the  pulse.  The  entire  absence  of  all  the  intoxication  symptoms 
of  septic  and  infectious  fevers,  such  as  the  benumbed  sensorium,  the  dry 
tongue  and  skin,  the  lessened  secretion  of  urine.  I  have  already  referred 
to  in  confirmation  of  the  belief  that  these  symptoms  are  not  dependent  upon 
the  rise  of  temperature.  Genzmer  and  Volkmann  assign  as  the  cause  of 
aseptic  traumatic  fever,  the  absorption  of  substances  resulting  from  the  dis- 
integration of  the  wounded  tissues  and  of  the  extravasated  blood,  and  state 
that  these  substances  probably  do  not  differ  markedly  from  those  produced 
by  physiological  tissue  metamorphosis.  This  explanation  certainly  has  re- 
ceived decided  support  by  the  experiments  which  I  have  described  in  this 
lecture,  a  large  part  of  which  have  been  performed  since  the  publication  of 
Genzmer  and  Volkmann's  article.  It  has  been  suggested  that  aseptic  trau- 
matic fever  is  a  reflex  neurosis,  and  this  suggestion  cannot  be  absolutely 
rejected  as  a  possible  explanation,  but  for  various  reasons,  which  cannot  here 
receive  further  consideration,  the  usually  accepted  explanation  is  the  more 
probable  one. 

"Genzmer  and  Volkmann:    Volkmann's  Sammlung,  No.  121. 


354  CARTWRIGHT  LECTURES 

An  instructive  case  of  ferment  intoxication  has  been  reported  by  Cramer.'" 
There  existed  in  a  young  woman  a  cyst,  the  size  of  a  goose's  egg,  between 
the  fibres  of  the  semitendinosus  muscle.  The  cyst  was  developed  from  a 
cavernous  angioma,  and  was  filled  with  dark  fluid  blood.  The  patient  had 
had  fever  for  almost  two  years  up  to  the  day  of  the  operation.  The  cause 
of  the  fever  could  not  be  discovered.  Immediately  after  the  removal  of  the 
cyst  the  fever  stopped  and  did  not  return.  In  this  case  the  cavernous  struc- 
ture of  the  cyst  wall  accounts  for  the  ease  with  which  we  must  suppose  a 
considerable  quantity  of  pyrogenic  substance  was  continuously  absorbed 
from  the  bloody  contents  of  the  cyst.  The  results  of  Angerer's  experiments, 
already  mentioned,  enable  us  to  explain  the  source  of  the  fever  in  this  case. 

Another  instance  may  be  cited  in  which  fever  is  probably  to  be  explained 
by  the  accumulation  within  the  body  of  products  of  normal  metabolism. 
More  or  less  fever  appears  to  be  a  constant  accompaniment  of  the  agonizing 
method  of  treatment  known  as  the  Schroth  cure.  In  this  treatment  the 
patient  is  kept  for  a  number  of  successive  days  on  dry  food  with  scarcely 
any  fluids.  Both  Bartels  and  Jiirgensen,"  who  have  investigated  the 
nutritive  changes  of  individuals  under  this  treatment,  believe  that  the  body 
becomes  so  poor  in  water  that  some  of  the  products  of  regressive  metamor- 
phosis cannot  be  carried  out  of  the  system.  This  certainly  seems  very  prob- 
able, and,  if  true  it  affords  in  the  light  of  recent  experiments  an  explanation 
of  the  accompanying  fever. 

I  believe  that  good  reasons  can  be  adduced  in  support  of  the  opinion  that 
the  febrile  conditions  sometimes  associated  with  leucocythaemia  profound 
anaemias  and  chlorosis  belong  to  the  group  of  fevers  we  are  now  considering. 
It  is  probable  that  some  of  the  obscure  ephemeral  fevers  are  also  to  be 
included  here.  But  to  consider  these  febrile  disorders  in  detail  would  lead 
us  into  the  domain  of  special  etiology  upon  which  we  have  already  perhaps 
encroached  too  far.  ISly  purpose  has  been  to  bring  before  your  attention 
only  a  few  clinical  examples  in  illustration  of  the  experimental  results. 

I  think  that  you  will  agree  with  me  in  the  conclusion  that  experimental 
and  clinical  evidence  justify  us  in  recognizing  as  a  distinct  group  of  pyro- 
genic agents  substances  which  have  no  necessary  connection  with  micro- 
organisms and  which  are  either  not  foreign  to  the  healthy  organism  or  are 
readily  formed  by  unorganized  ferments  from  normal  or  abnormal  con- 
stituents of  the  body.  These  substances  may  be  described  as  homologous  in 
distinction  from  the  heterologous  agents  concerned  in  the  production  of 
septic  and  infectious  fevers. 

"Cramer:    Verhandl.  d.  Deutschen  Gesellschaft  f.  Chirurgie,  13th  Congress, 
1884. 
•'  Jiirgensen:    Deutsches  Arch.  f.  klin.  Med.,  Bd.  I. 


GENERAL  PATHOLOGY  OF  FEVER         355 

A  class  of  pyrogenic  agents  of  far  greater  clinical  importance  than  those 
previously  considered  is  formed  by  the  products  of  microorganisms  which  in 
themselves  are  not  pathogenic.  A  considerable  number  of  bacteria  which 
when  inoculated  in  pure  culture  into  the  body  are  not  capable  of  further 
invasion  or  of  multiplication  produced  in  culture  fluids  and  in  dead  animal 
or  vegetable  material  poisonous  substances  often  of  great  virulence.  Excep- 
tion may  be  taken  to  the  description  of  these  organisms  as  non-pathogenic, 
inasmuch  as  the  products  of  their  activity  are  poisonous,  but  the  epithet 
pathogenic  is  usually  assigned  by  bacteriologists  only  to  such  microorgan- 
isms as  are  capable  of  multiplication  within  the  body.  If  we  called  all  of  the 
microorganisms  pathogenic  which  produce  poisonous  ptomaines  we  should 
have  to  include  in  this  category  a  far  larger  number  of  the  known  species 
of  bacteria  than  has  hitherto  been  customary. 

The  best  known  and  most  important  of  the  fevers  produced  by  chemical 
products  of  saprophytic  bacteria  are  those  grouped  under  the  name  putrid 
intoxication.  Until  the  introduction  of  the  modern  era  in  bacteriology  by 
Koch  nearly  all  of  the  experimental  work  on  the  etiology  of  fevers  related 
to  the  causation  of  the  septic  and  putrid  fevers.  It  is  instructive  with  our 
present  knowledge  to  follow  the  experiments  on  this  subject  from  the  period 
of  Gaspard,  Magendie,  and  Sedillot  up  to  recent  times.  What  light  has  been 
shed  upon  the  mass  of  contradictory  and  perplexing  results  of  experiments 
with  putrid  fluids  by  the  recent  chemical  and  biological  studies  of  putre- 
factive processes?  Some  of  the  putrid  substances  experimented  with 
undoubtedly  contained  parasitic  microorganisms,  and  others  contained  only 
obligatory  saprophytes.  Some  were  rich  in  poisonous  ptomaines,  and  others 
were  nearly  devoid  of  them.  The  whole  doctrine  of  the  parasitic  nature  of 
infectious  fevers  seems  to  have  hinged  in  the  minds  of  some  upon  the 
determination  of  the  question  whether  septic  and  putrid  fevers  are  produced 
by  the  absorption  of  chemical  substances,  or  by  the  invasion  of  pathogenic 
bacteria.  The  ideas  concerning  putrid  intoxication  dominated  at  one  time 
the  whole  field  of  fever  etiology,  and  were  applied  not  only  to  septicaemia 
but  to  typhoid  fever,  typhus  fever,  yellow  fever — in  fact,  to  nearly  all 
infectious  fevers.  ISTor  have  the  echoes  of  this  period  even  now  entirely 
died  out. 

Panum  was  the  first  to  isolate  from  putrid  materials  some  chemical  sub- 
stance or  substances  in  tolerable  purity,  certainly  free  from  bacteria.  This 
substance,  when  injected  into  animals,  produced  symptoms  of  putrid  intoxi- 
cation. Subsequently,  von  Bergmann  and  Schmiedeberg  isolated  from 
putrefying  yeast  a  poisonous  crystalline  substance,  their  celebrated  sepsin. 
For  a  time  the  opinion  prevailed  that  this  sepsin  is  the  source  of  all  putrid 
intoxications.    Thanks  to  the  investigations  of  Nencki  and  others,  and  par- 


356  CARTWEIGHT  LECTURES 

ticularly  of  Brieger,  we  now  know  that  many  alkaloidal  substances  can  be 
separated  from  putrefying  materials.  Some  of  these  so-called  cadaveric 
alkaloids  or  ptomaines  are  poisonous,  fever-producing,  others  are  harmless. 
There  is  no  reason  to  suppose  that  the  list  of  the  ptomaines  of  putrefaction 
has  been  exhausted,  nor  is  it  necessary  to  believe  that  all  of  the  poisonous 
constituents  of  putrefying  materials  of  an  alkaloidal  nature. 

Most  of  the  bacteria  concerned  in  ordinary  putrefactive  processes  are 
purely  saprophytic.  They  are  incapable  of  multiplication  in  the  living 
animal  tissues.  In  a  mixture  of  putrefactive  bacteria  it  is  not,  however, 
uncommon  to  find  genuine  pathogenic  or  parasitic  bacteria.  It  was  from 
such  sources  that  the  bacilli  of  mouse  septicaemia  and  of  rabbit  septicaemia 
(Koch)  were  obtained.  The  bacillus  of  malignant  oedema  is  also  often 
found  in  tlie  early  stages  of  post-mortem  decomposition. 

There  is,  of  course,  no  doubt  that  the  absorption  of  the  chemical  products  of 
putrefaction  may  produce  fever  with  septic  symptoms,  quite  independently 
of  the  penetration  and  multiplication  within  living  tissues  of  bacteria. 

Here  belong  certain  cases  usually  described  as  septic,  in  which  fever  and 
other  bad  symptoms  subside  upon  the  thorough  cleansing  and  disinfection 
of  a  foul  wound,  or  of  a  puerperal  uterus.  The  majority  of  cases  of  septi- 
caemia are  not  to  be  included  here,  for  they  depend  upon  the  invasion  of 
pathogenic  bacteria.  But,  excluding  the  cases  of  genuine  septicaemia,  there 
remain  the  putrid  intoxications  which  result  from  the  absorption  of  poison- 
ous substances  produced  in  necrotic  or  disintegrating  tissues,  or  exuda- 
tions, or  extravasated  blood,  by  the  action  of  purely  saprophytic  bacteria. 
The  ideas  which  I  have  expressed  on  this  subject  are  now  so  generally  ad- 
mitted that  they  require  no  further  elucidation. 

It  is  probable  that  fever,  with  symptoms  of  intoxication,  although  gen- 
erally of  a  much  milder  nature  than  in  the  class  of  cases  just  considered,  may 
be  produced  by  abnormal  fermentations  and  putrefactions  caused  by  sapro- 
phytic bacteria  in  the  alimentary  canal.  But  here  the  essential  morbid 
conditions  seem  to  be  abnormalities  in  the  gastric  and  intestinal  contents, 
due  partly  to  the  character  of  the  ingesta,  but  chiefly  to  alterations  of  the 
digestive  juices.  Fermentative  and  putrefactive  bacteria  are  normally  pres- 
ent in  the  intestinal  canal,  and  have  abundant  opportunities  to  gain  access 
to  this  situation.  The  number,  however,  which  can  multiply  and  thrive 
there  is  quite  limited,  for  under  normal  conditions,  according  to  Escherich, 
only  such  bacteria  can  multiply  to  any  extent  in  the  intestinal  canal  as  are 
capable  of  growing  with  little  or  no  oxygen,  and  of  deriving  their  nourish- 
ment from  the  anaerobic  fermentation  of  the  food  supplied  to  them  in  this 
situation.     Suitable  conditions  for  the  excessive  multiplication  of  putre- 


GENERAL  PATHOLOGY  OF  FEVER         357 

factive  or  fermentative  bacteria  may,  however,  be  furnished  by  abnormalities 
of  the  gastric  or  intestinal  contents. 

Of  a  far  more  serious  nature  are  the  putrid  or  ptomaine  intoxications 
which  result  from  the  ingestion  of  substances  which  have  undergone  outside 
of  the  body  putrefaction,  or  changes  which  lead  to  the  formation  of  poisonous 
ptomaines.  To  this  group  of  cases  belong  at  least  many  of  the  instances  of 
poisoning  which  have  been  caused  by  eating  certain  kinds  of  meat,  sausage, 
fish,  cheese,  etc.  In  some  of  these  instances  poisonous  ptomaines  have  been 
isolated  from  the  suspected  substances,  but  we  know  scarcely  anything  of 
the  microorganisms  which  are  concerned  in  their  production. 

It  is  important  to  bear  in  mind  that  it  is  not  stinking  putrefaction  alone 
which  gives  rise  to  poisonous  products.  Brieger  has  found  that  such  products 
may  be  absent  in  very  advanced  decomposition,  and  that  in  general  the  most 
virulent  products  are  formed  in  the  early  stages  of  putrefaction.  We  know, 
furthermore,  that  putrefactions  and  fermentations  differ  in  the  character  of 
their  products.  There  are  differences  according  to  the  kind  of  bacteria 
present,  according  to  the  substances  decomposed,  and  according  to  various 
other  conditions,  such  as  the  presence  of  oxygen,  the  temperature,  etc.  This 
is  not  the  proper  occasion  to  discuss  these  details. 

Enough  has  been  said  to  prove  that  we  are  justified  in  recognizing  as  a 
second  class  of  pyrogenic  agents  substances  which  are  the  products  of 
bacteria  in  themselves  not  pathogenic.  These  pyrogenic  agents  may  be 
formed  on  or  within  the  body,  or  they  may  be  produced  outside  of  the  body. 
I  would  not  by  any  means  have  you  infer  that  it  has  been  proven  in  all  of 
the  special  examples  which  I  have  mentioned,  that  the  bacteria  involved  are 
not  pathogenic,  or  capable  of  multiplication  within  the  living  tissues.  We 
have  not  sufficient  knowledge  to  assert  or  to  deny  this  in  every  instance,  but 
I  do  not  think  that  it  is  likely  exception  will  be  taken  to  the  classification 
which  I  have  adopted  for  most  of  these  cases.  As  has  repeatedly  been  men- 
tioned, our  purpose  here  is  not  an  analysis  of  individual  cases  of  fever,  but 
an  attempt  to  classify  systematically  the  various  pyrogenic  substances. 

We  come  now  to  the  third  and  most  important  group  of  fever-producing 
agents,  the  pathogenic  microorganisms.  So  overshadowing  is  their  impor- 
tance that  it  has  been  claimed  that  they  are  the  sole  causes  of  fever.  In 
contrast  with  former  times  it  is  no  longer  the  symptomatic  fevers  whose 
etiology  is  clearest.  We  have  much  more  definite  ideas  as  to  the  mode  of 
production  of  some  of  the  essential  fevers  which  were  once  the  most  obscure, 
than  we  have  of  symptomatic  fevers.  It  does  not  seem  to  me  worth  while  to 
go  over  the  chain  of  evidence  which  establishes  the  doctrine  that  the  infec- 
tious fevers  are  caused  by  microorganisms.  There  is  probably  no  one  who 
has  thoroughly  investigated  the  subject,  and  is  competent  to  form  an  opinion 


358  CARTWRIGHT  LECTURES 

on  it,  who  does  not  to-day  admit  that  a  number  of  infectious  diseases  have 
been  proven  to  depend  upon  specific  microorganisms,  and  that  it  is  a  logical 
inference  that  all  infectionus  diseases  are  caused  by  parasitic  organisms. 

It  is  not  germane  to  our  subject  to  enter  into  a  morphological  or  biological 
description  of  the  different  species  of  pathogenic  organisms  which  are 
causes  of  febrile  diseases.  The  only  question  which  concerns  us  in  this  con- 
sideration of  the  general  etiology  of  fever  is  how  the  microorganisms  produce 
fever.  Are  they  themselves  the  pyrogenic  agents,  or  do  they  produce  chemical 
substances  which  are  pyrogenic?  A  number  of  other  possibilities  might  be 
mentioned.  These  and  similar  questions  have  suggested  themselves  to  in- 
vestigators since  the  beginning  of  any  knowledge  of  parasitic  microorgan- 
isms. Our  information  is  far  from  sufficient  to  enable  us  to  answer  these 
questions  in  a  positive  manner,  and  still  we  are  not  left  wholly  to  vague 
surmises  in  attempting  to  form  some  sort  of  an  opinion. 

That  bacteria  can  produce  mechanical  effects  by  plugging  up  capillaries 
and  in  other  ways  is  certain,  but  the  wide  differences  presented  by  the  various 
infectious  diseases  cannot  be  reconciled  with  the  idea  that  pathogenic  bac- 
teria act  chiefly  by  mere  mechanical  interference  with  the  fluid  and  the  solid 
constituents  of  tlie  body.  Notwithstanding  the  fact  that  Strieker  and 
Albert  succeeded  in  producing  fever  by  the  injection  of  starch  granules  mto 
the  blood,  probably  no  one  will  be  inclined  to  attribute  the  pyrogenic  activity 
of  bacteria  in  any  considerable  extent  to  occlusion  of  bloodvessels. 

In  a  certain  number  of  infectious  diseases,  particularly  of  animals,  bacteria 
are  present  in  such  enormous  number  in  the  blood  and  tissues  that  some  are 
inclined  to  refer  the  disastrous  effects  of  the  organisms  to  the  withdrawal  of 
oxygen  and  other  nutritive  pabulum  from  the  cells  of  the  body.  So  far  as 
the  appropriation  of  oxygen  is  concerned,  this  idea  is  not  supported  by  the 
results  of  most  of  the  examinations  of  the  blood  in  cases  of  anthrax.  This 
explanation  was  more  popular  in  the  early  days  of  bacteriology  than  it  is 
at  present,  and  at  the  best  its  value  is  limited,  for  it  cannot  be  applied  to  a 
large  number  of  infectious  diseases,  such  as  cholera  or  typlioid  fever  where 
the  circulating  blood  is  not  largely  invaded  by  the  parasites.  Furthermore, 
it  is  not  clear  how  the  appropriation  by  bacteria  of  nutriment  intended  for 
the  tissues  would  help  us  to  explain  the  production  of  fever. 

It  has  been  suggested  that  the  increased  temperature  in  infectious  fevers 
may  be  explained  by  the  heat  produced  by  oxidation  or  other  cliemical 
changes  in  the  microorganisms  themselves.  But  this  is  not  at  all  a  satis- 
factory explanation.  Not  only  is  the  quantity  of  heat  which  can  come  from 
this  source  in  all  probability  very  small  compared  with  that  constantly  pro- 
duced in  the  body,  but  such  an  explanation  of  febrile  rise  of  temperature  is 


GENERAL  PATHOLOGY  OF  FEVER         359 

not  in  harmony  with  what  we  know  concerning  the  mode  of  production  of 
fever  (see  Lecture  I). 

The  failure  to  explain  the  pathogenic  power  of  bacteria  in  these  and 
similar  ways  led  to  the  supposition  that  the  morbid  activity  of  pathogenic 
bacteria  is  exerted  chiefly  by  means  of  injurious  chemical  products.  The 
demonstration  of  such  products  leaves  no  room  for  doubt  as  to  the  correct- 
ness of  this  supposition  for  some  infectious  diseases.  This  explanation  is 
probable  for  most  such  diseases,  but  experience  has  shown  that  it  is  particu- 
larly dangerous  to  indulge  in  hasty  generalization  in  this  department  of 
medical  science. 

Sterilized  and  filtered  cultures,  particularly  old  cultures,  of  various  patho- 
genic bacteria  are  capable  of  producing  fever  and  other  symptoms  when  in- 
jected into  the  blood  or  tissues.  This,  of  course,  makes  it  evident  that  the 
bacteria  in  question  give  rise  to  poisonous  substances.  It  is  necessary  to 
distinguish  between  the  intoxication  produced  by  the  injurious  products  of 
bacteria  and  the  infection  caused  by  multiplication  of  the  microorganisms 
within  the  body.  That  this  distinction  may  be  readily  overlooked  is  shown 
by  the  recent  experiments  with  the  inoculation  into  animals  of  pure  cultures 
of  the  typhoid  bacillus.  Small  quantities  of  these  cultures  may  be  inoculated 
without  any  apparent  effect;  if,  however,  larger  quantities  are  injected  into 
the  veins  or  the  peritoneal  cavity  of  a  rabbit,  the  animal  dies  in  a  short  time 
and  the  characteristic  bacilli  are  found  in  the  blood,  spleen,  and  elsewhere. 
It  was  supposed  by  Frankel  and  Simmonds,'"'  to  whom  we  owe  this  latter 
observation,  that  actual  infection  took  place,  but  it  has  been  demonstrated 
by  Sirotinin  and  by  Beumer  and  Peiper  **  that  under  these  circumstances  no 
multiplication  of  the  injected  bacilli  occurs,  and  that  the  same  results  may 
be  obtained  by  the  injection  of  sterilized  typhoid  cultures. 

The  isolation  in  a  chemically  pure  state  of  the  poisonous  products  of 
pathogenic  bacteria  encounters  great  difficulties,  and  we  owe  to  Brieger  ** 
nearly  all  that  has  been  accomplished  in  this  direction.  Two  substances 
which  he  has  obtained  from  cultures  of  pathogenic  bacteria  are  of  great 
interest.  Brieger  isolated  from  pure  cultures  of  the  typhoid  bacillus  a  very 
poisonous  ptomaine  or  toxine,  as  he  prefers  to  call  this  group  of  substances. 
He  has  given  to  it  the  name  typhotoxine.  It  may  be  somewhat  significant 
that  he  failed  to  find  typhotoxine  in  a  culture  which  had  stood  for  twenty- 
four  hours  at  a  temperature  of  102.2°  F.  (39°  C).    The  injection  of  typho- 

^  Frankel  and  Simmonds:  Die  Aetiologische  Bedeutung  des  Typhus-bacillus, 
Hamburg  und  Leipzig,  1886. 

"  Sirotinin:    Zeitschrift  f.  Hygiene,  Bd.  I,  465. 

Beumer  u.  Peiper:    Ihid,  p.  489. 
"Brieger:   Untersuchungen  iiber  Ptomaine,  Berlin,  1886. 


360  CAETWRIGHT  LECTUEES 

toxine  into  guinea-pigs  produced  great  muscular  weakness,  diarrhoea,  in- 
creased frequency  of  pulse  and  of  respiration,  and  death.  Nothing  is  said 
as  to  the  effect  upon  the  temperature  of  the  animal. 

A  toxine  has  been  isolated  by  Brieger  in  a  crystalline  form  from  an  im- 
pure culture  of  the  tetanus  bacillus.  This  substance,  called  tetaniu,  pro- 
duces, when  injected  into  animals,  the  characteristic  symptoms  of  tetanus. 

It  is  evident  that  these  important  discoveries  render  far  more  definite 
than  was  formerly  possible,  the  belief  that  bacteria  produce  fever  by  means 
of  their  chemical  products. 

A  dangerous  influence  exerted  by  poisonous  ptomaines  is  that  under  their 
agency  the  power  of  the  body  of  resisting  the  invasion  of  various  micro- 
organisms may  be  impaired  or  overcome.  Thus,  Wyssokowitsch  has  shown 
that  the  immunity  of  some  animals  against  certain  species  of  bacteria  may 
be  destroyed  by  ptomaine  poisoning. 

In  order  to  observe  the  effects  upon  the  temperature,  I  have  injected 
into  rabbits  sterilized  cultures  of  the  typhoid  bacillus.  Injections  of  very 
small  quantities  of  these  cultures  produce  no  effects,  somewhat  larger 
amounts  cause  a  rise  of  temperature  without  other  marked  symptoms,  still 
larger  quantities  produce  increased  temperature,  diarrhoea,  weakness,  and 
other  manifest  symptoms  of  severe  illness,  but  the  animal  may  recover; 
relatively  large  amounts  are  followed  by  fall  of  temperature,  grave  illness, 
and  death.  I  have  also  obtained  results  similar  to  those  of  Sirotinin,  who 
inoculated  two  rabbits  with  the  same  amount  of  a  typhoid  culture.  In  one 
rabbit  fever  developed  and  the  animal  recovered ;  in  the  other,  the  tempera- 
ture fell  after  the  injection,  and  the  animal  died.  This  certainly  does  not 
indicate  that  tlie  rise  of  temperature  in  itself  is  an  unwelcome  attendant  of 
intoxication  with  the  poisonous  products  of  bacteria.  My  experiments  cer- 
tainly showed  that  the  animals  were  more  likely  to  die  after  injection  of 
typhoid  cultures  when  the  temperature  fell  than  when  it  rose,  independently 
of  the  quantity  of  material  injected.  One  is  reminded  here  of  the  very 
malignant  cases  of  tyj)lioid  fever  reported  by  Friintzel,  and  others,  in  which 
the  temperature  throughout  a  great  part  of  the  disease  was  subfebrile,  or 
even  at  times  subnormal. 

In  no  disease  is  the  dependence  of  tbe  febrile  paroxysm  upon  the  presence 
of  bacteria  so  apparent  as  in  relapsing  fever,  where,  according  to  the  state- 
ments of  most,  although  not  of  all,  observers  the  spirilla  appear  in  the  blood 
at  the  beginning  of  a  paroxysm  and  disappear  at  the  end.  Whether  or  not, 
here  and  in  malaria,  the  pyrogenic  agent  is  a  chemical  product  of  the  micro- 
organisms causing  the  disease,  we  do  not  know, 

I  must  content  myself  with  having  brought  before  you  evidence  showing 
that  at  least  in  some  of  the  infectious  fevers  the  specific  bacteria  produce 


GEN^ERAL  PATHOLOGY  OF  FEVER  361 

pyrogenic  substances.  We  have  no  right  to  say  that  this  is  the  only  way  in 
which  pathogenic  bacteria  can  cause  fever. 

We  have  considered  now  three  groups  of  agents  concerned  in  the  produc- 
tion of  fever,  viz. :  first,  unorganized  ferments  and  other  relatively  homolo- 
gous substances;  second,  ptomaines  and  other  chemical  products  of  sapi:o- 
.phytic  microorganisms;  third,  pathogenic  microorganisms  and  their  chemi- 
cal products. 

It  is  not  to  be  understood  that  these  groups  correspond  to  sharply  defined 
classes  of  fever-producing  agents.  The  same  substance  may  be  produced  by 
the  action  of  unorganized  ferments,  as  well  as  by  saprophytic  bacteria  or  by 
parasitic  bacteria;  hence,  we  may  find  the  same  fever-producing  agent  in 
each  of  the  three  groups.  As  has  already  been  mentioned,  our  knowledge 
does  not  justify  us  in  regarding  these  various  substances  as  the  immediate 
and  direct  pyrogenic  agents.  The  epithet  pyrogenic  is  applied  to  them  only 
by  a  certain  latitude  of  signification.  It  is  possible  that  these  various  sub- 
stances, which  we  are  in  the  habit  of  describing  as  pyrogenic,  may  produce 
in  the  body  some  common  change  which  gives  rise  to  the  real  fever-producing 
agent.  This  is  the  view  of  von  Bergmann  and  Angerer,  who  believe  that  this 
common  change  is  a  liberation  of  fibrin  ferment  by  destruction  of  leucocytes. 
While  we  cannot  consider  this  view  as  more  than  an  hypothesis,  it  is,  never- 
theless, well  to  remember  that  apparently  heterogeneous  substances,  which 
are  usually  designated  as  pyrogenic,  may  produce  similar  changes  which  are 
to  be  regarded  as  the  real  source  of  the  febrile  disorder  of  animal  heat.  But, 
notwithstanding  these  limitations  and  these  elements  of  uncertainty,  it  seems 
to  me  that  some  such  classification  as  that  suggested  of  the  agents  producing 
fever  is  more  useful  than  that  usually  employed  in  the  discussions  of  the 
etiology  of  symptomatic  and  of  essential,  fevers. 

There  is  one  point  which  must  be  impressed  upon  every  one  who  makes 
many  experiments  with  pyrexial  agents.  This  is,  that  once  in  a  while  a 
substance  of  undoubted  pyrogenic  power  causes  a  fall  instead  of  a  rise  of 
temperature.  This  occurs  frequently  when  the  substance  is  injected  in  large 
quantity  and  under  these  circumstances  there  is  usually  produced  a  condi- 
tion of  collapse.  But  in  exceptional  cases  the  same  dose  which  will  cause  in 
one  animal  a  rise  of  temperature  may  give  rise  in  another  animal  of  the  same 
species  to  a  distinct  reduction  of  temperature.  In  these  latter  cases  there 
must  be  some  idiosyncrasy  on  the  part  of  the  animal.  Aronsohn  '^  refers  this 
unusual  phenomenon  to  some  peculiarity  of  the  heat  centers  in  the  brain,  and 
he  draws  an  interesting  parallel  between  this  contrary  effect  of  pyrogenic 
substances  and  the  exceptional  cases  in  which  antipyretic  drugs  give  rise  to 
elevation  instead  of  lowering  of  temperature. 

"Aronsohn:    Deutsche  med.  Wochenschrift,  1888. 
26 


362  CARTWRIGHT  LECTURES 

The  causes  of  fever  which  we  have  thus  far  discussed,  have  been  sub- 
stances wliich  exert  a  pyrogenic  effect  when  introduced  into  the  circulation. 
We  suppose  that  these  substances  act  in  some  way  upon  the  nervous  system, 
but  whether  or  not  this  action  is  a  primary  one  it  is  impossible  to  say.  Even 
if  we  assume,  as  is  often  done,  that  tliese  substances  incite  directly  in  the 
blood  and  tissues  chemical  changes  which  lead  to  increased  production  of 
heat,  we  must  still  have  recourse  to  some  action  upon  the  nervous  system,  as 
has  already  been  sufficiently  set  forth  in  the  previous  lectures. 

It  cannot  be  doubted  that  fever  may  be  caused  by  other  agencies  than 
pyrogenic  substances  present  in  the  blood  or  tissues.  The  effects  of  exposure 
to  external  heat  have  already  been  considered.  We  found  experimental 
evidence  in  support  of  the  view  ably  advocated  by  H.  C.  Wood,  that  in  typical 
cases  of  thermic  fever  or  sunstroke,  the  strain  placed  upon  the  heat-regulat- 
ing centres  by  exposure  to  excessive  heat  results  in  paralysis  of  these  centres 
with  rapid  elevation  of  the  internal  temperature. 

The  cause  of  the  elevation  of  temperature  in  tetanus  is  not  altogether 
clear.  In  this  disease  the  temperature  may  vary  but  little  from  the  normal, 
but  it  is  not  uncommon  to  find  excessive  elevations  of  temperature  toward 
the  termination.  Temperatures  of  113°  F.  (45°  C),  or  more,  have  been 
recorded.  The  idea  would  naturally  suggest  itself  that  the  rise  of  tempera- 
ture is  due  to  the  tetanic  muscular  spasms,  which  we  know  to  be  accompanied 
by  production  of  heat.  Leyden  was  led  to  adopt  this  explanation  by  the 
results  of  experiments  made  upon  animals.  He  succeeded  by  producing 
violent  tetanic  contractions  of  the  muscles  of  a  dog,  in  raising  the  internal 
temperature  in  the  course  of  one  hour  and  a  half  from  103.3°  F.  (39.0°  C.) 
to  112.6°  F.  (44.8°  C).  Clinical  observations,  however,  do  not  support  the 
supposition  that  the  hyperpyretic  temperatures  of  tetanus  are  dependent 
upon  the  muscular  contractions.  In  spite  of  violent  and  prolonged  tetanic 
spasms,  the  internal  temperature  may  remain  normal  or  be  but  slightly 
elevated.  There  is  a  decided  similarity  between  the  hyperpyrexia  of  tetanus 
and  that  which  occurs  in  rheumatism  and  some  other  diseases,  particularly 
in  affections  of  the  central  nervous  system,  and  it  certainly  seems  probable 
that  in  all  of  these  cases  there  is  a  profound  disturbance  of  the  heat-regulat- 
ing centres.  As  the  elimination  of  urea  in  tetanus  is  not  excessive,  we  find 
additional  reason  to  separate  tetanic  hyperpyrexia  from  ordinary  febrile  con- 
ditions. Recent  investigations  of  the  etiology  of  tetanus,  have  rendered  it 
certain  that  at  least  some  forms  of  this  disease  are  caused  by  infection  with 
a  special  microorganism.  This  has  been  demonstrated  not  only  in  the  tetanus 
of  animals  l)ut  also  in  that  of  human  beings.  The  tetanus  bacillus  has  been 
found  wide-spread  in  the  ground  in  Germany,  and  I  find  it  abundant  in  the 
ground  in  Baltimore  and  its  neighlwrliood.     In  experimental  tetanus,  the 


GENERAL  PATHOLOGY  OF  FEVEE         363 

bacillus,  which  has  not  yet  been  obtained  in  perfectly  pure  cultures,  develops 
chiefly  in  the  tissues  near  the  seat  of  innoculation,  and  does  not  invade  other 
parts  of  the  body  and  the  blood  to  any  great  extent.  This  indicates  that  the 
symptoms  are  referable  chiefly  to  poisoning  by  some  chemical  products  of 
the  specific  microorganism.  As  has  already  been  mentioned,  this  view  is 
sustained  by  Brieger's  discovery  in  cultures  containing  the  tetanus  bacillus 
of  a  peculiar  ptomaine  which  he  has  called  tetanin,  and  which  produces 
tonic  spasms  of  the  muscles.  It  is,  therefore,  reasonable  to  believe  that  the 
hyperpyrexia  of  tetanus  is  caused  by  the  action  of  poisonous  products  of  the 
tetanus  bacillus  on  the  nervous  centres  concerned  in  temperature  regulation. 
Our  present  knowledge,  however,  does  not  warrant  us  in  asserting  that  all 
forms  of  tetanus  in  human  beings  are  of  an  infectious  nature. 

In  the  first  lecture  of  this  course,  evidence  was  presented  to  show  that 
pyrexia  may  be  caused  by  affections  of  the  nervous  system  without  the  agency 
of  any  pyrogenic  substance.  It  may  jar  upon  the  sensibilities  of  some  to 
call  this  form  of  pyrexia  fever ;  but  this  hesitation  can  be  due  only  to  the  idea 
that  symptoms  which  are  referable  to  infection  or  intoxication  are  essential  to 
the  conception  of  fever.  In  my  judgment,  we  shall  be  led  into  confusion  if 
we  attempt  to  incorporate  into  our  definition  of  fever,  more  than  properly 
belongs  to  the  febrile  disorder  of  animal  heat,  and  from  this  point  of  view 
there  can  be  no  impropriety  in  designating  as  fever,  the  pyrexia  dependent 
directly  upon  affections  of  the  nervous  system. 

It  is  not  necessary  to  repeat  here  the  conclusive  experimental  evidence  for 
the  existence  in  the  nervous  system  of  centres  or  regions  which  control  the 
dissipation  of  heat  and  the  chemical  processes  concerned  in  the  production 
of  heat.  Those  who  are  not  much  impressed  by  experiments  upon  animals, 
can  hardly  fail  to  be  convinced  by  the  clinical  evidence  which  demonstrates 
that  lesions  of  the  nervous  system  may  cause  elevation  of  temperature,  which 
cannot  be  referred  to  the  action  of  any  pyrogenic  substance.  Such  evidence 
must,  of  course,  be  collected  from  cases  where  the  fever  cannot  be  explained 
by  inflammation,  bed-sores,  or  other  lesions  which  can  give  rise  to  absorption 
fever.  W.  Hale  White,**  in  the  interesting  article  already  referred  to,  has 
collected  a  number  of  cases  of  tumor,  hemorrhage,  softening,  sclerosis,  injury 
and  functional  disturbance  of  the  spinal  cord  and  brain,  in  which  the  pyrexia 
or  hyperpyrexia  is  to  be  explained  only  by  the  lesion  of  the  nervous  system. 
The  number  of  such  cases  might  be  considerably  increased.  These  cases 
show  that  lesions  of  the  cervical  part  of  the  cord,  of  the  pons,  of  the  corpus 
striatum,  and  of  the  neighboring  white  matter,  are  most  likely  to  be  asso- 
ciated with  high  temperature,  but  tbe  cases  hitherto  reported  hardly  justify 

'"W.  Hale  White:  The  Theory  of  a  Heat  Centre  from  a  Clinical  Point  of  View. 
Guy's  Hospital  Reports,  42,  1884. 


364  CARTWRIGHT  LECTURES 

positive  statements  as  to  the  exact  situation  in  man  of  thermically  active 
nerves  or  regions  in  the  brain  and  spinal  cord.  As  might  be  expected,  not 
only  focal  lesions,  but  also  diffuse  diseases  such  as  occur  in  general  paralysis 
of  the  insane,  locomotor  ataxia,  multiple  sclerosis  may  give  rise  to  pyrexia 
which  sometimes  assumes  the  form  of  temperature  crises.  It  is  in  harmony 
with  what  we  know  of  other  disorders  of  the  nervous  system,  to  find  that  not 
only  demonstrable  anatomical  lesions,  but  also  functional  disturbances  may 
produce  nervous  pyrexia.  Such  functional  disturbance  furnishes  the  most 
probable  explanation  of  the  singular  and  erratic  elevations  of  temperature 
which  have  been  occasionally  observed  in  hysteria. 

A  question  which  merits  more  consideration  than  it  is  possible  to  give  to 
it  on  the  present  occasion,  relates  to  the  possibility  of  the  occurrence  of  fever 
as  a  reflex  neurosis.  The  advance  in  our  knowledge  of  the  etiology  of  trau- 
matic and  inflammatory  fevers,  has  pushed  aside  almost  wholly  the  old 
doctrine  of  irritative  fever.  There  are,  however,  cases  of  fever  where  still 
the  simplest,  and  apparently  most  rational,  explanation  of  the  causation,  is 
peripheral  nerve  irritation.  As  examples  may  be  mentioned,  the  fever  re- 
sulting from  teething  in  children,  that  sometimes  accompanying  the  passage 
of  gall-stones  or  urinary  calculi,  and  that  occasionally  following  the  insertion 
of  a  catheter  into  the  urethra.  It  must  be  admitted  that  the  evidence  on  this 
point  is  not  conclusive.  Especially  is  there  lack  of  satisfactory  experimental 
evidence.  Electrical  irritation  of  the  exposed  sciatic  nerve  is,  under  ordinary 
circumstances,  followed  by  a  moderate  fall  of  temperature,  although  Ott" 
finds  that  in  atropinized  cats  such  irritation  is  followed  by  a  decided  rise 
of  temperature.  But  these  experiments  cannot  be  held  to  weigh  for  or 
against  the  doctrine  of  irritative  fever.  Observations  on  human  beings 
indicate  that  peripheral  nerve  irritation,  if  ever  a  cause  of  fever,  is  so  only 
in  certain  situations  and  under  certain  forms  of  stimulation,  and  in  certain 
individuals.  In  infants  temperature  regulation  is  more  labile  than  in  adults, 
so  that  it  may  be  that  nerve  irritation  can  more  readily  disturb  the  tempera- 
ture in  the  former  tlian  in  the  latter.  The  chief  controversy  as  to  the  ques- 
tion now  before  us,  has  been  as  to  the  explanation  of  certain  forms  of  urethral 
or  catheter  fever.  It  cannot  be  doubted  tluit  a  large  number,  probably  most, 
of  the  cases  of  so-called  urethral  fever,  are  instances  of  genuine  absorption 
fever.  Even  if  we  exclude  all  cases  with  diseased  kidneys,  or  with  cystitis 
or  other  inflammatory  disease  of  the  urinary  passages,  there  remains  a  cer- 
tain number  of  cases  in  wliich  the  gentle  insertion  of  a  disinfected  catheter 
is  followed  by  distinct  fel)rile  reaction.  It  seems  unwarrantable  to  assume 
that  in  all  of  those  cases  the  catheter  has  caused  a  laceration  of  the  urethra 

""Ott:    Therapeutic  Gazette,  August,  1887. 


GENEEAL  PATHOLOGY  OF  FEVER         365 

through  which  pyrogenic  substances  are  absorbed.  What  is  the  nature  and 
whence  the  source  of  these  substances?  In  the  cases  now  under  considera- 
tion, they  can  be  sought  only  in  the  normal  urine,  and  of  their  existence  there 
no  proof  has  been  afforded.  In  these  cases  it  is  certainly  very  difficult  to 
understand  how  the  fever  can  be  interpreted  as  due  to  the  absorption  of  some 
pyrogenic  agent,  and  faihng  this  explanation,  the  idea  that  the  fever  is 
dependent  upon  nerve  irritation  is  most  plausible. 

I  have  now  presented  to  you  an  imperfect  survey  of  the  general  etiology 
of  fever.  The  attempt  has  been  made  to  classify  the  leading  causes  of  fever, 
but  it  cannot  be  claimed  that  every  variety  of  fever  can  be  assigned  to  one 
of  these  groups  of  causes.  Our  knowledge  of  the  etiology  of  special  fevers 
is  still  too  imperfect  to  warrant  any  such  generalization.  Tliis  is  an  attrac- 
tive field  for  much  patient  investigation.  I  need  only  remind  you  of  the 
uncertainty  which  still  pertains  to  the  causation  of  many  of  the  fevers  of 
warm  countries.  There  is  reason  to  believe  that  there  remain  yet  to  be 
differentiated  etiologically,  specific  types  of  fever  which  occur  among  us,  and 
particularly  in  our  Southern  States.  It  may  be,  that  increasing  knowledge 
will  necessitate  the  recognition  of  varieties  of  pyrogenic  agents  entirely  dis- 
tinct from  any  with  which  we  are  now  familiar.  It  is  certain  that  future 
investigations  will  add  clearness  and  precision  to  our  ideas  of  the  nature  and 
mode  of  action  of  causes  of  fever  which,  at  the  best,  we  can  now  understand 
only  imperfectly. 

I  cannot  conclude  this  course  of  lectures  without  saying  a  few  words  on  a 
subject  which  must  engage  the  attention  of  every  one  who  gives  much  thought 
to  the  nature  of  fever.  What  is  the  significance  of  fever,  is  a  question  which 
thrusts  itself  upon  us  no  less  than  it  has  upon  physicians  in  all  ages.  Un- 
fortunately, we  cannot  to-day,  any  more  than  could  our  predecessors,  give 
other  than  a  speculative  answer  to  this  question.  There  have  been  in  all 
ages  enlightened  physicians  who  have  held  the  opinion  that  fever  is  a  process 
which  aids  in  the  elimination  or  destruction  of  injurious  substances  which 
gain  access  to  the  body.  Under  the  influence  of  ideas  which  sought  in  in- 
creased temperature  the  origin  of  the  grave  symptoms  of  fever,  we  have  in 
recent  times  in  great  part  lost  sight  of  the  doctrine  once  prevalent,  that  there 
may  be  in  fever  a  conservative  element.  There  is  much  which  speaks  in 
favor  of  this  doctrine.  The  real  enemy  in  most  fevers,  is  the  noxious  sub- 
stance which  invades  the  body,  and  there  is  nothing  to  prevent  us  from 
believing  that  fever  is  a  weapon  employed  by  nature  to  combat  the  assaults 
of  this  enemy.  The  doctrine  of  evolution  indicates  that  a  process  which 
characterizes  the  reaction  of  all  wann-blooded  animals  against  the  invasion 
of  a  host  of  harmful  substances,  has  not  been  developed  to  so  wide  an  extent, 
and  is  not  retained  with  such  pertinacit}^  without  subserving  some  useful 


366  CARTWRIGHT  LECTURES 

purpose.  This  is  a  point  of  view  from  which  many  pathological  processes 
can  be  regarded  with  advantage.  Even  suppuration,  which  one  does  not 
generally  look  upon  as  a  beneficent  provision,  is  a  most  important  instrument 
of  nature  in  forming  a  barrier  against  general  infection  of  the  body  with 
certain  microorganisms.  It  is  impossible  with  our  present  knowledge,  to 
say  in  exactly  what  way  fever  accomplishes  a  useful  purpose.  There  are 
facts  which  suggest  that  in  some  cases  of  fever  the  increased  temperature 
as  such  may  impair  the  vitality  or  check  the  virulence  of  patliogenic  micro- 
organisms, but  there  are  many  circumstances  which  make  it  difficult  to 
suppose  that  this  is  the  agency  by  which  fever  usually  exerts  a  favorable 
action. 

The  supposition  seems  to  me  more  probable  that  the  increased  oxidation 
of  fever  aids  in  the  destruction  of  injurious  substances.  According  to  this 
view,  the  fever-producing  agents  light  the  fire  which  consumes  them.  It  is 
not  incompatible  with  this  conception  of  fever,  to  suppose  that  the  fire  may 
prove  injurious  also  to  the  patient  and  may  require  the  controlling  hand  of 
the  physician.  Time  will  not  permit  me  to  elaborate  further  the  ideas  here 
suggested.  In  the  course  of  these  lectures  some  facts  have  been  presented 
and  others  might  be  drawn  from  clinical  and  experimental  observations 
which  favor  the  hypothesis  that  fever  is  in  a  certain  sense  a  conservative 
process.  Unproven  and  intangible  as  the  hypothesis  may  seem  to  some,  no 
apology  is  needed  for  bringing  to  your  attention  a  conception  of  fever  in 
favor  of  which  much  can  be  adduced,  and  which,  if  true,  is  of  fundamental 
importance,  both  tlieoretically  and  practically. 


HYPEETHERMY  IN  MAN' 

An  even  more  remarkable  case  has  been  reported  than  that  described  by 
Dr.  Jacobi.  It  was  reported  by  Dr.  W.  J.  Galbraith,  of  Omaha,  Neb.,  in  an 
article  entitled  "  A  Eemarkable  Case,"  and  published  in  the  "  Journal  of 
the  American  Medical  Association,"  March  31,  1891.  The  temperature  in 
this  case  was  observed  by  Dr.  Galbraith  to  rise  to  151°  F.,  while  the  nurse's 
record  shows  it  to  have  reached  171°  F.  The  patient  was  a  married  woman, 
twenty-six  years  of  age,  who  is  said  to  have  had  repeated  attacks  of  perito- 
nitis during  the  period  of  observation  of  the  high  temperature,  and  to  have 
passed  per  vaginam  over  one  thousand  pieces  of  bone,  which  were  believed 
to  come  from  "a  dead  foetus  of  extra-uterine  pregnancy.  Dr.  Galbraith's 
description  of  the  case  is  most  graphic.  At  first,  entirely  skeptical,  he 
refused  at  the  first  call  even  to  see  the  patient  in  consultation,  but  personal 
examination  later  made  a  complete  convert  of  him.  Suspecting  some  decep- 
tion, he  says  the  following  test  was  made :  "  The  patient  was  placed  in  a 
chair,  all  clothing  removed,  and  a  careful  examination  made  of  her  month 
and  axillary  region,  every  possible  precaution  taken  in  order  to  prevent  any 
deception,  and  holding  the  end  of  the  thermometer  so  that  it  could  not  be 
tipped  in  any  way,  we  again  proceeded  to  take  her  temperature ;  but,  gentle- 
men, the  result  was  the  same;  the  thermometer  under  the  axilla  registered 
137°  F.,  while  that  under  the  tongue  registered  131°  F." 

There  was  notliing  in  the  pulse  or  the  general  condition  of  the  patient  to 
indicate  any  elevation  of  temperature.  Especially  constructed  and  carefully 
tested  thermometers  were  used. 

So  far  as  one  can  judge  from  the  description  of  Dr.  Galbraith's  case,  and 
the  same  is  true  of  Dr.  Jacobi's  case,  there  was  no  apparent  mode  of  decep- 
tion. Still,  Dr.  Jacobi  must  pardon  me  if,  with  the  greatest  respect  for  his 
skill  as  an  observer,  I  express  complete  skepticism  as  to  the  trustworthiness 
of  these  observations.  I  do  not  undertake  to  explain  in  what  way  deception 
was  practised,  but  there  is  no  doubt  in  my  mind  that  there  was  deception. 
Such  temperatures  as  those  recorded  in  Dr.  Galbraith's  and  Dr.  Jacobi's 
cases  are  far  above  the  temperature  of  heat-rigor  of  mammalian  muscle  and 
are  destructive  of  the  life  of  animal  cells.    They  could  not  be  present  even  in 

*  Remarks  on  a  paper  by  A.  Jacobi,  before  the  Association  of  American  Physi- 
cians, Washington,  D.  C,  May  31,  1895. 

Tr.  Ass.  Am.  Physicians,  Phila.,  1895,  X,  189-191. 

367 


368  HYPEETHEEMY  IN"  MAN 

the  integument  alone  for  any  length  of  time  without  leaving  behind  mani- 
fest lesions  where  they  existed.  I  consider  them  to  be  physical  impossibili- 
ties under  the  conditions  described. 

[Addendum.  When  making  the  preceding  remarks  I  was  not  aware  that 
Dr.  Galbraith's  case  had  already  been  thoroughly  discredited  by  subsequent 
developments.  A  physician — Dr.  Bridges — who  happened  to  be  present 
when  I  was  speaking,  immediately  afterward  told  me  that  he  was  familiar 
with  the  case,  having  been  an  interne  in  the  hospital  where  this  woman  was 
admitted,  and  where  she  attempted  again  to  practise  deception,  which  was 
detected.  Two  articles  relating  to  the  case,  published  since  Dr.  Galbraith's 
article,  have  come  to  my  notice,  and  I  believe  that  Dr.  Bridges  referred  to  a 
third  article,  in  which  his  experiences  were  narrated ;  but  this  last  one  I  have 
not  seen.  One  article  is  by  Dr.  J.  E.  Summers,  Jr.,  in  the  "  Omaha  Clinic," 
September,  1891,  and  is  entitled  "  Omaha's  Eemarkable  Case  of  High 
Temperature — an  Undoubted  Hysterical  Fake."  The  patient's  temperature 
had  continued  to  oscillate  from  several  degrees  below  normal  to  any  point 
below  150°  F.,  with  symptoms  interpreted  as  those  of  peritonitis.  On  May 
19,  1891,  Dr.  Summers  performed  abdominal  section,  and,  save  the  presence 
of  old  adhesions  about  the  uterine  adnexa,  found  no  evidences  of  peritonitis 
or  of  the  previous  existence  of  an  extra-uterine  pregnancy.  Several  pieces 
of  bones  which  had  been  removed  from  the  vagina,  and  had  been  attributed 
to  a  macerated  foetus,  were  sent  to  Dr.  Billings,  at  the  Army  ]\Iedical 
Museum,  where  they  were  pronounced  to  be  ^'  portions  of  the  sternum  of 
some  bird,  probably  a  chicken;  also  one  of  the  long  bones  nearly  complete, 
and  a  portion  of  the  skull  of  a  chicken  or  some  bird  about  the  same  size. 
Other  fragments  are  of  larger  bones  than  those  of  a  fowl;  in  fact,  they  re- 
semble splinters  of  ordinary  beef  or  mutton  bones.  You  may  be  positively 
certain  tliat  none  of  the  fragments  of  bones  have  come  from  any  organism 
developed  in  a  human  female."  Before  sending  the  specimens  Dr.  Smnmers 
had  himself  come  to  the  conclusion  that  the  bones  were  not  those  of  a  human 
foetus,  but  had  been  placed  in  the  genital  passages  by  the  woman  herself. 
These  bones  are  still  preserved  in  the  Army  ]\Iedical  Museum,  where  I  have 
seen  them.  The  patient  had  "  never  been  able  to  make  her  temperature  go 
up,"  as  she  expressed  it,  when  Dr.  Summers  tested  it. 

A  second  article  was  published  in  February,  1892,  in  the  same  journal,  by 
Dr.  C.  T.  Poe,  entitled  "  A  Chronic  Malingerer."  Dr.  Poe  describes  his 
experience  with  this  patient  two  years  previous  to  the  pu])lieation  of  Dr. 
Calbraitli.  Dr.  Poe  narrates  a  remarkable  attempt  on  the  part  of  the  patient 
to  represent  that  she  had  recently  been  delivered  of  a  child,  although  ex- 
amination precluded  the  i)ossil)ility  of  this,  and  he  exposed  her  in  the  attempt 
to  palm  oil'  on  him  a  temperature  of  112°  F.    Here  the  trick  was  the  simple 


HYPERTHERMY  IN  MAN  369 

one  of  heating  the  thermometer  with  a  hot-water  bottle  in  the  bed.  I,t  may 
be  stated  that  in  the  fall  of  1889  this  versatile  malingerer  attended  a  course 
of  lectures  in  the  Woman's  ]\Iedical  College  at  Chicago.  There  were  many 
other  interesting  phenomena  of  malingering  presented  by  this  patient.  I 
am  not  aware  that  any  explanation  has  been  given  of  the  precise  method  by 
which  she  deceived  Dr.  Galbraith.  The  points  in  the  case  most  interesting 
to  me  are  not  the  extraordinary  height  of  the  temperature,  but  the  entire 
good  faith,  with  which  Dr.  Galbraith,  one  of  the  most  experienced  and  best- 
known  surgeons  in  Omaha,  reported  the  case,  and  the  apparent  thorougluiess 
of  the  tests  to  which  he  subjected  the  patient.] 


ADAPTATION  IN  PATHOLOGICAL  PROCESSES ' 

Grateful  as  I  am  for  the  personal  good-will  manifested  by  my  selection  as 
President  of  this  Congress,  I  interpret  this  great  and  unexpected  honor  as 
an  expression  of  your  desire  to  give  conspicuous  recognition  to  those  branches 
of  medical  science  not  directly  concerned  with  professional  practice,  and  as 
such  I  acknowledge  it  with  sincere  thanks. 

All  departments  represented  in  tliis  Congress  are  working  together  toward 
the  solution  of  those  great  problems — the  causes  and  the  nature,  the  preven- 
tion and  the  cure,  of  disease — whicli  have  always  been  and  must  continue 
to  be  the  ultimate  objects  of  investigation  in  medicine.  It  is  this  unity  of 
purpose  which  gives  to  the  history  of  medicine  from  its  oldest  records  to 
the  present  time,  a  continuity  of  interest  and  of  development  not  possessed 
in  equal  degree  by  any  other  department  of  knowledge.  It  is  this  same 
unity  of  purpose  which  joins  together  into  a  single,  effective  organism  the 
component  parts  of  this  Congress,  representing,  as  they  do,  that  principle 
of  specialization  and  subdivision  of  labor  which,  notwithstanding  its  perils, 
has  been  the  great  factor  in  medical  progress  in  modern  times. 

Medical  science  is  advanced  not  only  by  those  who  labor  at  the  bedside, 
but  also  by  those  who  in  tlie  laboratory  devote  themselves  to  the  study  of  the 
structure  and  functions  of  the  body  in  health  and  disease.  It  is  one  of  the 
most  gratifying  results  of  the  rapid  advance  in  medical  education  in  this 
country  during  the  last  few  years,  that  successful  workers  in  tlie  laboratory 
may  now  expect  some  of  those  substantial  rewards  which  formerly  were  to 
be  looked  for  almost  exclusively  in  the  fields  of  practical  medicine  and  sur- 
gery. We  already  have  abundant  assurance  that  the  steady  improvement 
in  opportunities  and  recompense,  and  other  material  conditions  essential  for 
the  prosecution  of  scientific  work  in  medicine,  will  enable  this  country  to 
contribute  to  the  progress  of  the  medical  sciences  a  share  commensurate  with 
its  great  resources  and  development  in  civilization. 

The  subject  of  "  Adaptation  in  Pathological  Processes,"  which  I  have 
selected  for  my  address  on  this  occasion,  is  one  which  possesses  the  broadest 
biological,  as  well  as  medical,  interests.  It  is  this  breadth  of  scientific  and 
practical  interest  that  must  justify  my  choice  of  a  theme  which  involves 

'  President's  address  before  the  Congress  of  American  Physicians  and  Surgeons, 
Washington,  D.  C,  May  5,  1897. 

Tr.  Cong.  Am.  Phys.  &  Surg..  N.  Haven,  1897,  IV.  284-310. 
.370 


ADAPTATION  IN  PATHOLOGICAL  PROCESSES  371 

many  technical  considerations  and  many  problems  among  the  most  obscure 
and  unsettled  in  the  whole  range  of  biology  and  of  medicine. 

I  shall  employ  the  epithet  "  adaptive  "  to  describe  morbid  processes  which 
bring  about  some  sort  of  adjustment  to  changed  conditions  due  to  injury  or 
disease.  In  view  of  the  more  technical  and  restricted  meaning  sometmies 
attached  to  the  term  "  adaptation  "  in  biology,  objection  may  be  made  to 
this  broad  and  general  application  of  the  word  in  pathology;  but  no  more 
suitable  and  convenient  epithet  than  "  adaptive  "  has  occurred  to  me  to 
designate  the  entire  group  of  pathological  processes  whose  results  tend  to 
the  restoration  or  compensation  of  damaged  structure  or  function,  or  to  the 
direct  destruction  or  neutralization  of  injurious  agents.  Processes  which 
may  be  described  variously  as  compensatory,  regenerative,  self-regulatory, 
protective,  healing,  are  thus  included  under  adaptive  pathological  processes. 
These  processes  are,  in  general,  more  or  less  advantageous  or  useful  to  the 
individual;  but  for  reasons  which  will  be  stated  later  the  conception  of 
pathological  adaptation  and  that  of  advantage  to  the  individual  are  not 
wholly  coextensive. 

Within  the  limits  of  an  address  I  cannot  hope  to  do  more  than  direct 
attention  to  some  of  those  aspects  of  the  subject  which  seem  to  me  to  be  of 
special  significance.  Although  most  striking  examples  of  adaptation  are  to 
be  sought  in  comparative  and  vegetable  pathology,  what  I  shall  have  to  say 
will  relate  mostly  to  human  pathology.  My  purpose  is  not  to  point  out  the 
beauties  or  the  extent  of  adaptations  in  pathological  processes,  but  rather 
to  say  something  concerning  the  general  mechanism  of  their  production 
and  the  proper  attitude  of  mind  regarding  them,  and  to  illustrate  the  general 
principles  involved  by  a  few  representative  examples. 

It  has  been  contended  that  the  conception  of  adaptation  has  no  place  in 
scientific  inquiry;  that  Ave  are  justified  in  asking  only  by  what  means  a 
natural  phenomenon  is  brought  about,  and  not  what  is  its  meaning  or  pur- 
pose; in  other  words,  that  the  only  question  open  to  scientific  investigation 
is  How  ?  and  never  Why  ?  I  hope  to  make  clear  by  what  follows  in  what  light 
I  regard  this  question,  and  in  this  connection  I  shall  simply  quote  Lotze, 
who,  beginning  as  a  pathologist,  became  a  great  philosopher :  "  Every 
natural  phenomenon  may  be  investigated  not  only  with  reference  to  the 
mathematical  grounds  of  its  possibility  and  the  causes  of  its  occurrence,  but 
also  as  regards  the  meaning  or  idea  which  it  represents  in  the  world  of 
phenomena." 

The  most  wonderful  and  characteristic  attribute  of  living  organisms  is 
their  active  adaptation  to  external  and  internal  conditions  in  such  a  way 
as  tends  to  the  welfare  of  the  individual  or  of  the  species.  Of  the  countless 
physiological  examples  which  miglit  be  cited  to  illustrate  this  principle,  I 


372    ADAPTATION  IX  PATHOLOGICAL  PEOCESSES 

select,  almost  at  random,  the  presen'ation  of  the  normal  temperature  of  the 
body  in  warm-blooded  animals  under  varying  external  temperatures  and 
varying  internal  production  of  heat,  the  regulation  of  respiration  according 
to  the  need  of  the  tissues  for  oxygen,  the  influence  of  the  load  upon  the  work 
performed  by  muscles,  the  accommodation  of  the  heart  to  the  work  demanded 
of  it,  the  response  of  glands  to  increased  functional  stimulation,  the  adjust- 
ment of  the  iris  to  varying  degrees  of  illmnination,  the  influence  of  varying 
etatic  conditions  upon  the  internal  architecture  of  bone. 

The  most  striking  characteristic  of  these  countless  adaptations  is  their 
apparent  purposefuLiiess.  Even  if  it  be  true,  as  has  been  said  by  Lange,  that 
"  the  formal  purposefuhiess  of  the  world  is  nothing  else  than  its  adaptation 
to  our  understanding,"  it  is  none  the  less  true  that  the  human  mind  is  hO 
constituted  as  to  desire  and  seek  an  explanation  of  the  adaptations  which  it 
finds  everywhere  in  organic  nature.  Prom  the  days  of  Empedocles  and  of 
Aristotle  up  to  the  present  time  there  have  been  two  leading  theories  to 
explain  the  apparent  purposefulnessof  organic  nature — the  one,  the  tele- 
ological,  and  the  other,  the  mechanical  theory.  The  teleological  theory,  in 
its  traditional  signification,  implies  something  in  the  nature  of  an  intelli- 
gence working  for  a  predetermined  end.  So  far  as  the  existing  order  of 
nature  is  concerned,  the  mechanical  theory  is  the  only  one  open  to  scientific 
investigation,  and  it  forms  the  working  hypothesis  of  most  biologists.  This 
theor}',  in  its  modem  form,  seeks  an  explanation  of  the  adaptations  of  living 
beings  in  factors  concerned  in  organic  evolution.  What  these  factors  are  we 
know  only  in  part.  Those  which  are  most  generally  recognized  as  operative 
are  variation,  natural  selection,  and  heredity.  That  additional  factors,  at 
present  little  understood,  are  concerned  seems  highly  probable.  The  accep- 
tance of  the  explanation  of  physiological  adaptations  furnished  by  the  doc- 
trine of  organic  evolution  helps  us,  I  believe,  in  the  study  of  pathological 
adaptations. 

As  the  word  "  teleology  "  has  come  to  have,  in  the  minds  of  many,  so  bad 
a  repute  in  the  biological  sciences,  and  as  I  desire,  without  entering  into  any 
elaborate  discussion  of  the  subtle  questions  here  involved,  to  avoid  miscon- 
ceptions in  discussing  subjects  whose  ultimate  explanation  is  at  present 
beyond  our  ken,  I  shall  here  briefly  state  my  opinion  that  all  of  those  vital 
manifestations  to  which  are  applied  such  epithets  as  adaptive,  regulatory, 
regenerative,  compensatory,  protective,  are  the  necessary  results  of  the  action 
of  forms  of  energy  upon  living  matter.  The  final  result,  however  useful 
and  purposeful  it  may  be,  in  no  way  directly  influences  the  chain  of  events 
which  leads  to  its  production,  and,  therefore,  the  character  of  the  result 
affords  no  explanation  whatever  of  the  mechanism  by  which  the  end,  whether 
it  appear  purposeful  or  not,  has  been  accomplished.    In  every  case  the  ulti- 


ADAPTATION  IN  PATHOLOGICAL  PROCESSES  373 

mate  aim  of  inquiry  is  a  mechanical  explanation  of  the  process  in  question. 
Notwithstanding  valuable  contributions,  especially  within  recent  years, 
toward  such  mechanical  explanations,  we  are  still  far  removed  from  the 
attainment  of  this  aim. 

The  knowledge  of  the  fact  that  the  living  body  is  possessed  of  means 
calculated  to  counteract  the  effects  of  injurious  agencies  which  threaten  or 
actually  damage  its  integrity  must  have  existed  as  long  as  the  knowledge  of 
injury  and  disease,  for  the  most  casual  observation  teaches  that  wounds  are 
repaired  and  diseases  are  recovered  from.  It  is  no  part  of  my  present  purpose 
to  trace  the  history  of  the  numerous  speculations  or  even  of  the  development 
of  our  exact  knowledge  concerning  the  subjects  here  under  consideration.  I 
cannot  refrain,  however,  from  merely  referring  to  the  important  role  which 
the  conception  of  disease,  as  in  some  way  conservative  or  combative  in  the 
presence  of  harmful  influences,  has  played  from  ancient  times  to  the  present 
in  the  history  of  medical  doctrines.  Whole  systems  of  medicine  have  been 
founded  upon  this  conception,  clothed  in  varying  garb.  There  is  nothing 
new  even  in  the  image,  so  popular  nowadays,  representing  certain  morbid 
processes  as  a  struggle  on  the  part  of  forces  within  the  body  against  the 
attacks  of  harmful  agents  from  the  outer  world.  Indeed,  Stahl's  whole  con- 
ception of  disease  was  that  it  represented  such  a  struggle  between  the  anima 
and  noxious  agents.  What  lends  especial  interest  to  these  theories  is  that 
then,  as  now,  they  profoundly  influenced  medical  practice  and  were  the 
origin  of  such  well-known  expressions  as  vis  medicatrix  naturae  and  medicus 
est  minister  naturae. 

It  is  needless  to  say  that  there  could  be  no  exact  knowledge  of  the  extent 
of  operation  or  of  the  nature  of  processes  which  restore  or  compensate 
damaged  structures  and  functions  of  the  body  or  combat  injurious  agents, 
before  accurate  information  was  gained  of  the  organization  and  workings 
of  the  body  in  health  and  in  disease.  Although  the  way  was  opened  by 
Harvey's  discovery  of  the  circulation  of  the  blood,  most  of  our  precise 
knowledge  of  these  subjects  has  been  obtained  during  the  present  century, 
through  clinical  observations  and  pathological  and  biological  studies.  In 
the  domain  of  infectious  diseases  wonderful  and  hitherto  undreamed-of  pro- 
tective agencies  have  been  revealed  by  modem  bacteriological  discoveries. 
Here,  as  elsewhere  in  medicine,  the  experimental  method  has  been  an  in- 
dispensable instrument  for  discoveries  of  the  highest  importance  and  for  the 
comprehension  of  otherwise  inexplicable  facts.  Very  interesting  and  sug- 
gestive results,  shedding  light  upon  many  of  the  deeper  problems  concerning 
the  nature  and  power  of  response  of  living  organisms  to  changed  conditions, 
have  been  obtained  in  those  new  fields  of  experimental  research  called  by 
Roux  the  mechanics  of  development  of  organisms,  and  also  in  part  designated 


374  ADAPTATION  IN  PATHOLOGICAL  PROCESSES 

physiological  or  experimental  morpholog:y.  Although  we  seem  to  be  as  far 
removed  as  ever  from  the  solution  of  the  most  fundamental  problem  in 
biology,  the  origin  of  the  power  of  living  beings  to  adjust  themselves  actively 
to  internal  and  external  relations,  we  have  learned  something  from  these 
investigations  as  to  the  parts  played  respectively  by  the  inherited  organiza- 
tion of  cells  and  by  changes  of  internal  and  external  environment  in  the 
processes  of  development,  growth,  and  regeneration. 

In  physiological  adaptations,  such  as  those  which  have  been  mentioned, 
the  cells  respond  to  changed  conditions,  to  meet  which  they  are  especially 
fitted  by  innate  properties,  determined,  we  must  believe,  in  large  part  by 
evolutionary  factors.  In  considering  pathological  adaptations  the  question 
at  once  suggests  itself  whether  the  cells  possess  any  similar  peculiar  fitness 
to  meet  the  morbid  changes  concerned;  whether,  in  other  words,  we  may 
suppose  that  evolutionary  factors  have  operated  in  any  direct  way  to  secure 
for  the  cells  of  the  body  properties  especially  suited  to  meet  pathological 
emergencies.  Can  we  recognize  in  adaptive  pathological  processes  any 
manifestations  of  cellular  properties  which  we  may  not  suppose  the  cells  to 
possess  for  physiological  uses?  This  question  appears  to  me  to  be  of  con- 
siderable interest.  I  believe  that  it  can  be  shown  that  most  pathological 
adaptations  have  their  foundation  in  physiological  processes  or  mechanisms. 
In  the  case  of  some  of  these  adaptations,  however,  we  have  not  sufficiently 
clear  insight  into  the  real  nature  of  the  pathological  process  not  into  all  of 
the  physiological  properties  of  the  cells  concerned  to  enable  us  to  give  a  posi- 
tive answer  to  the  question. 

Wliile  we  must  believe  that  variation  and  natural  selection  combined  with 
heredity  have  been  important  factors  in  the  development  and  maintenance 
of  adjustments  to  normal  conditions  of  environment,  it  is  difficult  to  see 
how  they  could  have  intervened  in  any  direct  way  in  behalf  of  most  patho- 
logical adaptations. 

An  illustration  will  make  clear  the  points  here  involved.  Suppose  the 
human  race,  or  any  species  of  animal,  to  lack  the  power  to  compensate  the 
disturbance  of  the  circulation  caused  by  a  damaged  heart-valve,  and  that  an 
individual  should  happen  to  be  born  with  the  exclusive  capacity  of  such 
compensation.  The  chances  are  that  there  would  arise  no  opportunity  for 
the  display  of  this  new  capacity,  and  it  is  inconceivable  that  the  variety 
would  be  perpetuated  tlirough  the  operation  of  the  law  of  survival  of  the 
fittest  by  natural  selection,  unless  leaky  or  clogged  heart-valves  became  a 
common  character  of  the  species.  When,  however,  we  learn  that  the  dis- 
turbance of  circulation  resulting  from  disease  of  the  heart-valves  is  com- 
pensated by  the  performance  of  increased  work  on  the  part  of  the  heart,  and 
that  it  is  a  general  law  that  such  prolonged  extra  work  leads  to  growth  of 


ADAPTATION  IN  PATHOLOGICAL  PROCESSES  375 

muscle,  we  see  at  once  that  this  compensation  is  only  an  individual  instance 
of  the  operation  of  a  capacity  which  lias  abundant  opportunities  for  exercise 
in  normal  life,  where  the  influence  of  natural  selection  and  other  factors  of 
evolution  can  exert  their  full  power. 

In  a  similar  light  we  can  regard  other  compensatory  and  functional 
pathological  hypertrophies — indeed,  I  believe,  also  to  a  considerable  extent 
the  pathological  regenerations,  inflammation,  and  immunity,  although  here 
the  underlying  factors  are,  of  course,  different. 

We  may,  however,  reasonably  suppose"  that  natural  selection  may  be 
operative  in  securing  protective  adjustments,  such  as  racial  immunity, 
against  morbific  influences  to  which  living  beings  are  frequently  exposed 
for  long  periods  of  time  and  through  many  generations. 

These  considerations  help  us  to  explain  the  marked  imperfections  of  most 
pathological  adaptations  as  contrasted  with  the  perfection  of  physiological 
adjustments,  although  I  would  not  be  understood  to  imply  that  the  absence 
of  the  direct  intervention  of  natural  selection  in  the  former  is  the  sole  ex- 
planation of  this  difference.  The  cells  are  endowed  with  innate  properties 
especially  fitted  to  secure  physiological  adaptations.  No  other  weapons  than 
these  same  cells  does  the  body  possess  to  meet  assaults  from  without,  to 
compensate  lesions,  to  restore  damaged  and  lost  parts.  But  these  weapons 
were  not  forged  to  meet  the  special  emergencies  of  pathological  conditions. 
Evolutionary  factors  have  not  in  general  intervened  with  any  direct  reference 
to  their  adaptation  to  these  emergencies.  Such  fitness  as  these  weapons 
possess  for  these  purposes  comes  primarily  from  properties  pertaining  to 
their  physiological  uses.  They  may  be  admirably  fitted  to  meet  certain 
pathological  conditions,  but  often  they  are  inadequate.  Especially  do  we 
miss  in  pathological  adjustments  that  co-ordinated  fitness  so  characteristic 
of  physiological  adaptations.  So  true  is  this  that  the  propriety  of  using 
such  terms  as  compensation  and  adaptation  for  any  results  of  pathological 
processes  has  been  questioned. 

A  heart  hypertrophied  in  consequence  of  valvular  lesion  does  not  com- 
pletely restore  the  normal  condition  of  the  circulation.  Experience  has 
shown  that  a  kidney  hypertrophied  in  consequence  of  deficiency  of  the  other 
kidney  is  more  susceptible  to  disease  than  the  normal  organ.  What  an  in- 
complete repair  of  defects  is  the  formation  of  scar-tissue,  and  with  what 
inconveniences  and  even  dangers  may  it  be  attended  in  some  situations ! 
If  we  look  upon  inflammation  as  an  attempt  to  repair  injury,  and,  therefore, 
as  an  adaptive  process,  with  what  imperfections  and  excesses  and  disorders 
and  failures  is  it  often  associated !  How  often  in  some  complex  pathologi- 
cal process,  such  as  Bright's  disease  or  cirrhosis  of  the  liver,  can  we  detect 
some  adaptive  features,  attempts  at  repair  or  compensation,  but  these 
overshadowed  l)y  disorganizing  and  harmful  changes ! 


376  ADAPTATION  IN^  PATHOLOGICAL  PROCESSES 

It  is  often  difficult  to  disentangle,  in  the  complicated  processes  of  disease, 
those  elements  which  we  may  appropriately  regard  as  adaptive  from  those 
which  are  wholly  disorderly  and  injurious.  There  are  usually  two  sides 
fo  the  shield,  and  one  observer  from  his  point  of  view  may  see  only  the  side 
of  disorder,  and  another  from  a  different  point  of  view,  only  that  of 
adaptation. 

The  conception  of  adaptation  in  a  pathological  process  is  not  wholly 
covered  by  that  of  benefit  to  the  individual,  I  understand,  as  has  already 
been  said,  by  an  adaptive  pathological  process  one  which  in  its  results 
brings  about  some  sort  of  adjustment  to  changed  conditions.  This  adjust- 
ment is  usually,  wholly  or  in  part,  advantageous  to  the  individual;  but  it 
is  not  necessarily  so,  and  it  may  be  harmful.  The  closure  of  pathological 
defects  by  new  growths  of  tissue  is  a  process  which  must  be  regarded  as 
adaptive.  But  one  would  hardly  describe  as  advantageous  the  scar  in  the 
brain  which  causes  epilepsy.  A  new  growth  of  bone  to  fill  in  defects  is  often 
highly  beneficial ;  but  what  grave  consequences  may  result  from  thickening 
of  the  skull  to  help  fill  the  space  left  by  partial  arrest  in  development  of 
the  brain  in  embryonic  life  or  infancy !  We  see  here,  as  everywhere,  that 
"  Nature  is  neither  kind  nor  cruel,  but  simply  obedient  to  law,  and,  there- 
fore, consistent." 

In  turning  now  to  the  more  special,  but  necessarily  fragmentary,  con- 
sideration of  a  few  of  the  pathological  processes  in  which  adaptation,  in 
the  sense  defined,  is  more  or  less  apparent,  I  shall  have  in  view  the  answers 
to  those  two  questions,  What  is  the  meaning  of  the  process?  and  How 
is  it  caused  ?  which  confront  us  in  our  investigation  of  all  natural  phenomena. 
At  the  outset  it  must  be  admitted  that  our  insight  into  the  nature  of  many 
of  these  processes  is  very  imperfect,  and  that  here  answers  to  the  world-old 
riddles  Why?  and  How?  are  correspondingly  incomplete  and  liable  to  err. 

Although  almost  all  of  the  elementary  morbid  processes,  even  the  degen- 
erations and  death  of  cells,  may,  under  certain  conditions  of  the  body,  serve 
a  useful  purpose — the  pre-eminent  examples  of  pathological  adaptation,  in 
the  sense  of  restoration  or  compensation  of  damaged  structure  or  function, 
or  the  direct  destruction  or  neutralization  of  injurious  agents,  are  to  be 
found  among  the  compensatory  hypertrophies,  the  regenerations,  and  the 
protective  processes.  To  this  last  ill-defined  group  I  refer  parasiticidal  and 
antitoxic  phenomena,  and  some  of  the  manifestations  of  inflanmiation,  and 
perhaps  also  of  fever.  In  the  last  analysis  tliese  protective  processes,  no  less 
than  the  otiiers  mentioned,  must  depend  upon  the  activities  of  cells. 

As  it  is  manifestly  impossible,  within  the  limits  of  a  general  address,  to 
attempt  a  detailed  consideration  of  any  large  number  of  these  adaptive  path- 
ological processes,  and  as  such  consideration  would  necessarily  involve  tlie 


ADAPTATION  IN  PATHOLOGICAL  PROCESSES  377 

discussion  of  many  technical  and  doubtful  points,  I  have  thought  that  my 
purpose  would  be  best  served  by  the  selection  of  a  few  representative  ex- 
amples. 

The  compensatory  hypertrophies  afford  admirable  illustrations  of  certain 
fundamental  principles  regarding  adaptations  in  pathology  which  I  have 
already  stated.  The  hypertrophy  secures  a  functional  adjustment,  often  of 
a  highly  beneficial  character,  to  certain  morbid  conditions.  This  useful 
purpose  is  attained  by  a  succession  of  events  determined  from  beginning  to 
end  of  the  necessary  response  of  cells  and  tissues,  in  consequence  of  their 
inherent  organization,  to  the  changed  conditions.  Given  tlie  changed  con- 
ditions, on  the  one  hand,  and  the  organization  of  the  cells,  on  the  other,  the 
result  must  follow  as  surely  as  night  follows  day,  and  this  final  result  in- 
fluences the  preceding  series  of  events  no  more  in  the  one  case  than  in  the 
other.  That  the  cells  possess  the  particular  organization  determining  the 
manner  of  their  response  to  these  changed  conditions,  and,  therefore,  the 
beneficial  character  of  the  result,  is  dependent  upon  innate  properties  whose 
fitness  for  the  purpose  doubtless  has  been  largely  fixed  by  evolutionary 
factors,  operating,  however,  mainly  in  behalf  of  physiological  functions  and 
not  directly  toward  pathological  adjustments.  In  correspondence  with  this 
view  we  find  that  our  knowledge  of  the  manner  of  production  of  the  com- 
pensatory hypertrophies  of  various  organs  and  tissues  stands  in  direct 
relation  to  our  knowledge  of  the  physiology  of  the  same  organs  and  tissues. 

Those  compensatory  hypertrophies  into  the  mechanism  of  whose  produc- 
tion we  have  the  clearest  insight  are  referable  to  increased  functional  activity, 
and  are,  therefore,  spoken  of  as  work-hypertrophies.  This  has  been  proved 
for  the  muscular  hypertrophies  and  compensatory  hypertrophy  of  the  kidney ; 
but  the  demonstration  is  not  equally  conclusive  for  the  compensatory  hyper- 
trophy of  other  glands.  I  know,  however,  of  no  instance  in  which  this  factor 
in  the  explanation  can  be  positively  excluded. 

The  relationship  between  increased  functional  activity  and  hypertrophy 
is  so  evident  in  many  cases  that  there  is  strong  presumption  in  favor  of  this 
explanation  of  those  glandular  compensatory  hypertrophies  which  have  not 
as  yet  been  clearly  referred  to  the  class  of  functional  hypertrophies.  The 
very  occurrence  of  compensatory  hypertrophy  of  an  organ  may  direct  atten- 
tion to  the  fact  that  it  is  endowed  with  definite  functions,  and  the  conditions 
under  which  the  hypertrophy  occurs  may  shed  light  upon  the  nature  of  these 
functions.  I  need  only  remind  you  of  the  significance,  from  this  point  of 
view,  of  the  compensatory  hypertrophy  of  the  thyroid,  adrenal,  pituitary, 
and  other  glands  with  internal  secretions,  I  fail  to  see  why  Nothnagel 
should  consider  a  priori  improbable  the  occurrence  of  compensatory  hyper- 
trophy of  one  sexual  gland  after  loss  of  the  other,  even  before  sexual  ma- 
27 


378  ADAPTATION  IN  PATHOLOGICAL  PROCESSES 

turity,  or  why  Ribbert,  who  has  apparently  demonstrated  experimentally 
such  an  occurrence,  should  find  it  necessary  to  seek  the  explanation  in  reflex 
nervous  influences  or  mere  hyperaemia.  The  so-called  secondary  sexual 
characters  and  the  changes  following  castration,  including  the  influence  upon 
a  hypertrophied  prostate,  point  to  important,  even  if  little  imderstood,  func- 
tions which  for  the  present  we  can  perhaps  best  attribute  to  so-called  internal 
secretions  of  these  sexual  organs. 

The  name  compensatory  hypertrophy  is  sometimes  applied  to  growths  of 
tissue  that  merely  t-ake  the  place  of  another  kind  of  tissue  which  has  fallen 
out,  as,  for  example,  the  growth  of  adipose  tissue  around  a  shrunken  kidney 
or  pancreas,  or  between  atrophied  muscle-fibres.  Here  there  is  only  com- 
pensation of  space,  but  no  compensation  of  structure  or  function.  Such 
hypertrophies  and  growths  are  described  better  as  complementary  than  com- 
pensatory. 

Familiar  examples  of  pathological  hypertrophies  from  increased  work 
are  the  hypertrophy  of  the  heart  from  valvular  disease  and  other  causes, 
that  of  the  muscular  coats  of  canals  and  bladders  behind  some  obstruction, 
and  that  of  one  kidney  after  loss  or  atrophy  of  the  other. 

In  order  to  understand  fully  the  manner  of  production  of  work-hyper- 
trophy of  a  part  resulting  from  some  morbid  condition,  it  is  essential  to  know 
the  nature  of  the  disturbances  induced  by  the  imderlying  morbid  condition, 
how  these  disturbances  excite  increased  functional  activity  of  the  part  which 
becomes  hypertrophied,  and  what  the  relation  is  between  this  greater  activity 
and  the  increased  growth  of  the  part. 

It  is  impossible  on  this  occasion  to  go  through  the  whole  list  of  compen- 
satory hypertrophies  with  reference  to  the  application  of  these  principles. 
In  no  instance  can  the  requirements  stated  be  completely  met  in  the  present 
state  of  our  knowledge.  It  will  suffice  for  an  understanding  of  the  principles 
involved,  and  it  is  only  with  these  that  I  am  now  concerned,  if  I  take  a  con- 
crete example.  I  select  the  classical  and  best  studied  one — compensatory 
hypertrophy  of  the  heart.  I  trust  that  I  shall  be  pardoned  for  selecting  so 
commonplace  an  illustration,  as  the  main  points  involved  must  be  familiar 
to  most  of  my  audience;  but  it  is  possible  that  the  application  made  of  them 
may  not  be  equally  fiimiliar.  The  only  matters  essential  to  my  present  hne 
of  argument  are  the  mechanism  of  production  of  the  hypertrophy  and  the 
general  character  of  the  adaptation  tliereby  secured. 

The  heart,  like  other  organs  of  the  body,  does  not  work  ordinarily  up  to 
iii  full  capacity,  but  it  is  capable  of  doing  at  least  three  or  four  times  its 
ut^ual  work.  The  excess  of  energy  brought  into  play  in  doing  this  extra 
work  is  called  conveniently,  although  not  without  some  impropriety,  "  re- 
serve force."     It  has  been  proved  experimentally  that  this  storehouse  of 


ADAPTATION  IN  PATHOLOGICAL  PROCESSES  379 

reserve  power  is  sufficient  to  enable  the  healthy  heart,  at  least  that  of  a  dog, 
to  accommodate  itself  at  once  or  after  a  few  beats  to  high  degrees  of  in- 
sufficiency or  obstruction  at  its  valvular  orifices  without  alteration  in  the 
mean  pressure  and  speed  of  the  blood  in  the  arteries.  But  even  so  tireless 
and  accommodating  an  organ  as  the  heart  cannot  be  driven  at  such  high 
pressure  without  sooner  or  later,  becoming  fatigued,  and  consequently  so 
dilated  as  to  fail  to  meet  the  demands  upon  it.  If  it  is  to  continue  long  the 
extra  work,  it  n^ust  receive  new  increments  of  energy. 

The  cardiac  muscle  is  far  less  susceptible  to  fatigue  than  the  skeletal 
muscles,  but  that  it  may  become  fatigTied  seems  to  me  clear. 

Leaving  out  of  consideration  some  doubtful  causes  of  cardiac  hypertrophy, 
such  as  nervous  influences,  the  various  morbid  conditions  which  lead  to  this 
affection  are  such  as  increase  either  the  volume  of  blood  to  be  expelled  with 
each  stroke,  or  the  resistance  to  blood-flow  caused  by  the  pressure  in  the 
arteries  or  by  narrowing  at  one  of  the  valvular  orifices,  or  both.  Unless 
some  regulating  mechanism  steps  in,  each  of  these  circulatory  disturbances 
must  increase  the  resistance  to  contraction  of  the  cardiac  muscle,  and  it  is 
evident  that  the  heart  must  do  extra  work  if  it  is  to  pump  the  blood  through 
th6  arteries  with  normal  pressure  and  speed.  It  is,  however,  no  explanation 
of  this  extra  work  simply  to  say  that  it  occurs  because  there  is  demand  for  it. 
Increased  work  by  the  heart  in  cases  of  disease  of  its  nutrient  arteries  would 
often  meet  a  most  urgent  demand  on  the  part  of  the  body,  but  here  the  heart 
flags  and  fails. 

The  physiologists  have  given  us  at  least  some  insight  into  the  mechanism 
by  which  the  heart  responds  through  increased  work  to  the  circulatory  dis- 
turbances which  have  been  mentioned.  These  disturbances  all  increase  the 
strain  on  the  wall  of  one  or  more  of  the  cavities  of  the  heart ;  in  other  words, 
increase  the  tension  of  the  cardiac  muscle,  in  much  the  same  way  as  a  weight 
augments  the  tension  of  a  voluntary  muscle.  Now  it  is  a  fundamental  physi- 
ological law  that  with  a  given  stimulus  greater  tension  of  a  muscle,  within 
limits,  excites  to  more  powerful  contraction,  and  thus  to  the  performance 
of  greater  work.  It  seems  clear  that  this  law  applies  to  the  muscles  of  the 
heart,  as  well  as  to  voluntary  muscle.  We  do  not  know  precisely  how  in- 
creased tension  facilitates  the  expenditure  of  greater  muscular  energy. 

Anotlier  well-known  fact  in  the  mechanics  of  muscle  is  of  importance  in 
this  connection.  With  increase  of  muscular  tension  under  a  given  stimulus 
g,  point  is  reached  where  the  extent  of  contraction  is  diminished,  although 
the  mechanical  work  done,  determined  by  multiplying  the  height  to  which 
the  load  is  lifted  by  the  weight  of  the  load,  is  increased.  This  law  applied 
to  the  heart,  whose  contractions  are  always  maximal  for  the  conditions 
present  at  any  given  time  signifies  that,  with  increased  resistance  to  the 


380  ADAPTATION  IX  PATHOLOGICAL  PROCESSES 

contraction  of  the  muscular  wall  of  one  of  its  cavities,  this  cavity  will  empty 
itself  during-  systole  less  completely  than  before.  In  other  words,  dilatation 
occurs,  and,  as  lias  been  shown  by  Roy  and  Adami,  to  whom  we  owe  important 
contributions  on  this  as  well  as  on  many  other  points  relating  to  the  me- 
chanics of  the  heart,  dilatation  regularly  antedates  hypertrophy.  This 
primary  dilatation,  however,  is  not  to  be  looked  upon  as  evidence  of  beginning 
heart-failure,  for,  as  these  investigators  have  pointed  out,  it  is  within  limits 
only  an  exaggeration  of  a  physiological  condition,  and  can  be  subsequently 
overcome  by  hypertrophy,  which,  in  consequence  of  increase  in  the  sectional 
area  of  the  muscle,  lessens  the  strain  upon  each  fibre,  and  thereby  permits  it 
to  shorten  more  during  contraction.  If  this  result  is  completely  secured, 
we  have  simple  hypertrophy.  More  often  the  dilatation  remains,  and  must 
necessarily  remain,  and  we  have  eccentric  hypertrophy,  which  secures,  for 
a  time  at  least,  adequate,  but  I  do  not  think  we  can  say  perfect,  compensation. 

The  weight  of  existing  evidence  favors  the  view  that  the  power  of  the 
heart  to  adapt  its  work  to  the  resistance  offered  resides  primarily  in  its 
muscle-cells,  and  not  in  intrinsic  or  extrinsic  nervous  mechanisms,  although 
doubtless  these  latter  in  various  ways,  which  cannot  be  here  considered,  in- 
fluence and  support  this  regulating  capacity.  Nor  can  I  here  pause  to  dis- 
cuss the  influence  of  blood-supply  to  the  cardiac  muscle  upon  the  force  of 
ventricular  contraction,  although  Porter  has  demonstrated  that  this  is 
important. 

In  tracing  the  steps  from  the  primary  morbid  condition  to  the  final  hyper- 
trophy, we  have  thus  far  had  to  deal  mostly  with  known  mechanical  factors. 
We  now  come  to  the  question,  How  does  increased  functional  activity  lead  to 
increased  growth? 

Inasmuch  as  greater  functional  activity  is  regularly  associated  with  a 
larger  supply  of  blood  to  the  more  active  part,  the  view  is  advocated  by  many 
that  the  increased  growth  is  the  direct  result  of  this  hyperaemia,  and  one 
often  encounters,  especially  in  biological  literature,  this  opinion  expressed 
as  if  it  were  an  indisputable  fact.  There  is,  however,  no  conclusive  proof 
of  this  doctrine,  and  many  facts  speak  against  it.  Tlie  examples  from  human 
pathology  commonly  cited  to  support  the  doctrine  that  local  active  hyper- 
aemia incites  growth  of  cells  are,  so  far  as  I  am  able  to  judge,  complicated 
with  other  factors,  such  as  injury,  inflammation,  or  trophic  disturbances. 
Transplantation-experiments,  such  as  John  Hunter's  grafting  the  cock's 
spur  upon  the  cock's  coml),  sometimes  adduced  in  this  connection,  are  not 
decisive  of  this  question,  for  here  a  new  circumstance  is  introduced  which 
some  suppose  to  be  the  determining  one  for  all  morbid  cell-growth,  namely, 
the  disturbance  of  the  normal  equilibrium  between  parts.  Local  active 
hyperaemia  may  exist  for  a  long  time  without  evidence  of  increased  growtli 


ADAPTATION  m  PATHOLOGICAL  PEOCESSES  381 

in  the  congested  part.  To  say  that  the  hyperaemia  must  be  functional  is 
at  once  to  concede  tliat  it  is  not  the  sole  factor.  Experiments  from  Bizzo- 
zero's  laboratory,  by  Morpurgo  and  by  Penzo,  indicate  that  local  hyperaemia 
due  to  vaso-motor  paralysis,  or  to  the  application  of  heat,  favors  cell-multi- 
plication in  parts  where  proliferation  of  cellS  is  a  normal  phenomenon  or  is 
present  from  pathological  causes,  but  that  it  is  incapable  of  stimulating  to 
growth  cells  whose  proliferating  power  is  suspended  under  physiological 
conditions,  as  in  developed  connective  tissue,  muscles,  and  the  kidneys. 

It  has  been  usually  assumed  that  the  way  in  which  local  hyperaemia  may 
stimulate  cell-growth  is  by  increasing  the  supply  of  nutriment  to  cells. 
The  trend  of  physiological  investigation,  however,  indicates  that  the  cell 
to  a  large  extent  regulates  its  own  metabolism.  If  the  cell  needs  more  food, 
of  course  it  cannot  get  it  unless  the  supply  is  at  hand,  and  in  this  sense  we 
can  understand  how  a  larger  supply  of  blood  may  be  essential  to  increased 
growth ;  but  this  is  a  very  different  thing  from  saying  that  the  augmented 
blood-supply  causes  the  growth. 

It  is  by  no  means  clear  that  the  question  as  to  the  influence  of  increased 
blood-supply  upon  cell-growth  is  identical  with  that  of  increased  lymph- 
supply.  The  experiments  of  Paschutin  and  of  Emminghaus,  from  Ludwig's 
laboratory,  nearly  a  quarter  of  a  century  ago,  indicate  that  local  hyperaemia 
due  to  vaso-motor  paralysis  does  not,  as  a  rule,  increase  tlie  production  of 
lymph ;  and  more  recent  experiments,  although  not  wholly  concordant  in  their 
results  upon  this  point,  tend  to  the  same  conclusion.  Functional  activity, 
however,  has  a  marked  influence  in  increasing  the  quantity  and  affecting  the 
quality  of  lymph  in  the  active  part.  Our  knowledge  of  the  physical  and 
chemical  changes  in  working  muscles  and  glands  enables  us  to  conceive  why 
this  should  be  so,  for  all  are  now  agreed  that  the  formation  of  lymph  is  due 
not  simply  to  filtration  from  the  blood-plasma,  but  also  to  diffusion,  and 
some  believe  likewise  to  active  secretion  by  the  capillary  endothelium. 
Doubtless  arterial  hyperaemia  is  essential  to  the  maintenance  of  the  increased 
flow  of  lymph  in  working  organs. 

There  are  difficulties  in  the  way  of  supposing  that  increased  supply  of 
lymph  in  itself  furnishes  the  explanation  of  cell-growth,  and  especially  of 
that  which  characterizes  hypertrophy  of  muscles  and  glands.  Pathologists 
have  frequent  opportunities  to  study  the  effects  of  all  degrees  of  increased 
production  and  circulation  of  lymph  associated  with  venous  hyperaemia.  A 
kidney  or  a  muscle  may  from  this  cause  he  subjected  for  months  and  years 
to  an  excess  of  lymph-flow,  but  there  is  no  demonstration  of  any  consequent 
hypertrophy  or  hyperplasia  of  renal  epithelium  or  muscle-cell.  It  is  true 
that  the  chemical  composition  of  the  lymph  is  not  the  same  as  that  of  lymph 
resulting  from  increased  function,  and  it  is  possible  that  in  this  chemical 


382  ADAPTATION  IX  PATHOLOGICAL  PROCESSES 

difference  lies  the  kernel  of  the  whole  matter.  It  may  also  be  urged  that  in 
venous  hyperaemia  there  are  circumstances  which  restrain  or  prevent  growtli. 
Nevertheless,  if  overfeeding,  merely  in  consequence  of  increased  supply  of 
nutriment,  were  the  real  explanation  of  work-hypertrophies,  one  would 
expect  to  find  some  evidence  of  this  in  the  class  of  cases  mentioned. 

Kibbert  has  recently  given  a  new  shape  to  the  doctrine  that  local  hyper- 
aemia excites  growth.  While  rejecting  the  usual  explanation  that  it  does 
so  by  supplying  more  food,  he  contends  that  distention  of  the  blood  vessels 
and  lymph-spaces,  by  mechanically  disturbing  the  mutual  relations  of  parts, 
removes  obstacles  to  growth.  This  theory  cannot  be  advantageously  dis- 
cussed until  the  fact  is  first  established  that  uncomplicated  local  hyperaemia 
does  incite  growth. 

As  the  matter  now  stands,  it  seems  to  me  that  any  satisfactory  explana- 
tion of  the  cell-growth  causing  work-hypertrophies  must  start  from  physical 
or  chemical  changes  in  the  muscle-  or  gland-cell  itself  directly  connected 
with  the  increased  function.  These  changes  are  the  jn-imum  mobile,  and, 
however  important  increased  supply  of  blood  or  lymph  may  be  in  the  subse- 
quent chain  of  events,  it  is  not  the  determining  factor.  The  whole  problem 
is  part  of  the  general  one  of  the  causes  of  pathological  cell-growth,  to  which 
I  shall  have  occasion  to  refer  again. 

It  is  interesting  to  note  that  not  all  kinds  of  excess  of  functional  activity 
lead  to  hypertrophy.  A  heart  may  beat  for  years  faster  than  normal  with- 
out becoming  hypertrophied.  Small  movements  of  muscle,  often  repeated, 
do  not  cause  hypertrophy.  It  would  appear  that  the  amount  of  work  done 
in  each  functional  act  must  attain  a  certain  height  in  order  to  stimulate 
growth.  On  the  other  hand,  if  the  muscle  be  stretched  beyond  certain  limits, 
it  does  not  hypertrophy ;  on  the  contrary,  it  may  atropliy,  as  may  l)e  seen  in 
greatly  distended  canals  and  cavities  with  muscular  walls.  This  behavior 
is  also  in  accordance  with  physiological  observations. 

The  compensatory  hypertrophy  of  muscle  seems  to  be  due  mainly  to 
increase  in  the  size  of  cells,  although  there  are  observations  indicating  that 
they  may  also  multiply.  That  of  most  glands  is  referable  to  increase  both 
in  number  and  size  of  cells.  Within  four  or  five  days  after  extirpation  of  a 
kidney  karyokinetic  figures  may  be  found  in  increased  number  in  the  cells 
of  tlie  remaining  kidney. 

The  general  character  of  the  adaptation  secured  by  compensatory  hyper- 
trophy of  the  heart  is  sufficiently  well-known.  I  wish  to  point  out  certain 
of  its  imperfections.  I  shall  not  dwell  upon  the  well-known  abnormal  con- 
ditions, with  their  remote  consequences,  of  tiie  systemic  or  pulmonary  circu- 
lation, wliich  are  present  during  the  stage  of  compensation,  nor  shall  I  speak 
of  the  various  circumstances  which  may  interfere  with  the  establishment  of 
compensatory  hypertrc)j)liy. 


ADAPTATION"  IN  PATHOLOGICAL  PEOCESSES  383 

The  muscle  of  a  hypertrophied  heart  is  sometimes  compared  to  that  of 
the  blacksmith's  arm,  and  the  statement  is  made  that  there  is  no  reason 
inherent  in  the  muscle  itself  why  the  one  should  fail  more  than  the  other. 
This  may  be  true,  but  it  is  not  self-evident.  Exercise  may  influence  in 
various  ways  the  nutrition,  function,  and  growth  of  muscle  as  well  as  of  other 
parts.  Mere  increase  in  bulk  is  a  coarse  effect.  Quality  may  be  improved  as 
well  as  quantity.  The  biggest  muscle  is  not  necessarily  the  best  or  the  most 
powerful.  As  every  trainer  knows,  various  conditions  under  which  work  is 
done  influence  the  result.  Increase  in  the-  reserve  energy  of  the  heart,  secured 
by  judicious  exercise — and  this  is  the  main  factor  in  endurance — probably 
cannot  be  attributed  mainly  to  hypertrophy;  indeed,  enlargement  of  this 
organ  from  exercise  is  often  a  serious  condition.  Much  more  might  be  said 
in  this  line  of  thought,  but  I  have  indicated  why  it  seems  to  me  unjustifiable 
to  assume,  without  further  evidence,  that  the  condition  of  the  muscle  in 
pathological  hypertrophies  is  necessarily  identical  in  all  respects  with  that 
in  physiological  hypertrophies. 

There  is  an  important  difference  in  the  working-conditions  between  most 
hypertrophied  hearts  and  the  normal  heart.  Altliough  the  maximal  available 
energy  of  a  hypertrophied  heart  during  compensation  is  greater  than  that  of 
the  normal  heart,  clinical  experience  shows  that  in  the  majority  of  cases  the 
energy  available  for  unusual  demands — that  is,  the  so-called  reserve  force — 
is  less  in  the  former  than  in  the  latter.  Sometimes,  especially  when  the 
hypertrophy  has  developed  in  early  life,  the  hypertrophied  heart  is  at  no 
disadvantage  in  this  respect.  As  pointed  out  with  especial  clearness  by 
Martins,  the  significance  of  this  alteration  in  the  ratio  normally  existing 
between  the  energy  expended  for  ordinary  needs  and  that  available  for 
unusual  demands,  is  that  it  furnishes  an  explanation  of  the  greater  liability 
of  the  hypertrophied  heart  to  tire  upon  exertion.  Fatigue  of  the  heart  is 
manifested  by  dilatation  of  its  cavities,  and  when  this  dilatation  from  fatigue 
is  added  to  that  already  existing  in  most  cases,  relative  insufficiency  of  the 
mitral  or  tricuspid  valve  is  likely  to  occur,  and  the  compensation  is,  at  least 
for  a  time,  disturbed.  The  circulation  through  the  coronary  arteries,  whose 
integrity  is  so  important  for  the  welfare  of  the  heart,  is  impaired,  and  a 
vicious  circle  may  be  established.  Notwithstanding  the  valuable  contribu- 
tions from  the  Leipzig  clinic  as  to  the  frequency  of  various  anatomical  lesions 
in  the  muscle  of  hypertrophied  hearts,  it  does  not  seem  to  me  necessary  to 
have  recourse  to  them  as  an  indispensable  factor  in  the  explanation  of  the 
breakage  of  compensation ;  but  I  shall  not  here  enter  into  a  discussion  of  the 
general  subject  of  tlie  causes  of  failure  of  compensation. 

I  have  described  with  some  detail,  although  very  inadequately,  the  manner 
of  production  of  compensatory  hypertrophy  of  the  heart,  in  order,  by  this 


384  ADAPTATION"  IN  PATHOLOGICAL  PKOCESSES 

representative  example,  to  make  clear  what  seem  to  me  to  be  certain  general 
characteristics  of  many  adaptive  pathological  processes,  and  I  beg  here  to 
call  attention  especially  to  the  following  points.  As  has  been  emphasized 
by  Nothnagel  and  others,  no  teleological  idea  or  form  of  language  need  enter 
into  the  explanation  of  the  mechanism  of  the  process.  The  final  result  is 
the  necessary  consequence  of  the  underlying  morbid  conditions.  We  have 
satisfactory  mechanical  explanations  for  essential  steps  in  the  process,  and 
there  is  no  reason  to  assume  that  other  than  mechanical  factors  are  con- 
cerned in  those  vital  manifestations  which  at  present  we  are  unable  to  ex- 
plain by  known  physical  and  chemical  forces.  The  properties  of  the  cells 
which  determine  the  character  of  their  response  to  the  changed  conditions 
are  none  other  tlian  their  well-known  physiological  properties.  The  adapta- 
tion finally  secured,  admirable  as  it  is  in  many  respects,  and  perhaps  adequate 
for  long  and  active  life,  is  generally  attended  with  marked  imperfections, 
and  strictly  speaking,  is  not  a  complete  compensation.  It  does  not  present 
that  co-ordinate  and  special  fitness  which  we  are  accustomed  to  find  in 
physiological  adaptations,  for  the  explanation  of  which  so  much  has  been 
gained  by  the  study  of  the  factors  concerned  in  organic  evolution. 

It  may  be  argued  that  under  the  circumstances  no  better  kind  or  degree 
of  adaptation  can  be  conceived  of  than  that  which  actually  occurs,  and  that 
the  operation  of  evolutionary  factors,  with  especial  reference  to  the  adjust- 
ment of  the  organism  to  the  conditions  causing  cardiac  hypertrophy,  could 
not  secure  any  better  result.  I  think  that  it  is  not  difficult  to  conceive  how 
improvements  might  be  introduced.  It  is,  however,  permissible  to  suppose 
that  the  introduction  into  the  workings  of  the  organism  of  some  better 
mechanism  to  compensate  the  morbid  conditions,  might  be  at  the  sacrifice 
of  more  important  physiological  attributes  of  the  body.  ^lore  perfect  path- 
ological adaptations  might  in  many  instances  involve  a  deterioration  of  the 
physiological  cliaracters  of  the  species.  It  is  often  the  case  that  the  more 
highly  organized  living  beings  lack  some  capacity  possessed  by  those  lower 
in  the  scale  of  organization  to  resist  or  compensate  injury  and  disease.  This 
is  notably  true  of  the  power  to  regenerate  lost  parts.  It  is,  however,  along 
the  lines  of  improvement  in  the  physiological  characters  of  the  individual 
or  species  that  tbe  opportunity  often  lies  for  securing  increased  resistance 
to  disease  or  better  pathological  adaptations. 

It  would  be  interesting  to  continue  our  consideration  of  the  compensatory 
hypertrophies  by  an  examination  of  tliose  of  glandular  organs  from  points 
of  view  similar  to  those  adopted  for  the  heart.  For  the  kidney,  at  least,  the 
materials  are  at  hand  for  such  a  purpose;  but,  as  I  desire,  in  the  limited 
time  at  my  disposal,  to  touch  upon  otlier  varieties  of  pathological  adaptation, 
I  must  refer  those  interested  especially  to  the  investigations  of  Grawitz  and 


ADAPTATION  IN  PATHOLOGICAL  PROCESSES  385 

Israel,  Ribbert,  Nothnagel,  and  Sacerdotti  as  to  the  conditions  underlying 
compensatory  hypertrophy  of  the  kidney.  I  can  likewise  merely  call  atten- 
tion to  the  interesting  researches  of  Ponfick  upon  the  most  wonderful  of  the 
compensatory  hypertrophies  in  higher  animals,  that  of  the  liver.  Ponfick, 
as  is  well  known,  has  demonstrated  that  after  removal  of  three-fourth  of  this 
organ  new  liver-substance,  with  normal  functions,  is  recreated  from  the  re- 
mainder and  to  an  amount  nearly  equalling  that  which  was  lost. 

The  chapter  of  pathological  adaptations  in  bones  and  joints  I  shall  leave 
untouched,  notwithstanding  the  admirable  illustrations  which  might  be 
drawn  from  this  domain. 

There  is  no  more  fascinating  field  for  the  study  of  pathological  adapta- 
tions with  reference  to  the  mechanical  factors  involved  than  that  furnished 
by  the  blood  vessels,  as  has  been  shown  especially  by  the  brilliant  researches 
of  Thoma.  With  wonderful  precision  can  a  vessel  of  system  of  vessels  adjust 
itself  to  changes  in  the  pressure,  velocity,  and  quantity  of  blood,  and  thereby 
serve  the  needs  of  the  tissues  for  blood.  Under  pathological,  as  well  as 
physiological  conditions,  this  adjustment  may  be  brought  about  not  only 
through  the  agency  of  vaso-motor  nerves  and  the  physical  properties  of  the 
vascular  wall,  but  also,  when  the  necessity  arises,  by  changes  in  the  structure 
of  the  wall. 

The  changes  in  the  circulation  introduced  by  the  falling  out  of  the  placen- 
tal system  at  birth  are  essentially  the  same  as  those  resulting  from  amputa- 
tion of  an  extremity,  and  the  consequent  alterations  in  the  structure  of  the 
umbilical  artery  are  identical  with  those  in  the  main  artery  of  the  stump 
after  amputation.  The  closure  of  the  ductus  Botalli  and  the  ductus  venosus 
soon  after  birth,  and,  still  better,  transformations  of  vessels  in  the  embryo, 
furnish  physiological  paradigms  for  the  development  of  a  collateral  circu- 
lation. Many  other  illustrations  might  be  cited,  did  time  permit,  to  show 
that  in  the  processes  of  normal  development,  growth  and  regressive  meta- 
morphosis of  parts,  both  before  and  after  birth,  and  in  menstruation  and 
pregnancy,  changed  conditions  of  the  circulation  arise  analogous  to  certain 
ones  observed  under  pathological  circumstances,  and  tliat  the  mode  of  adjust- 
ment to  these  changes  by  means  of  anatomical  alterations  in  the  vessels  may 
be  essentially  the  same  in  the  physiological  as  in  the  morbid  state.  I  see  in 
these  facts  an  explanation  of  the  relative  perfection  of  certain  vascular 
adaptations  to  pathological  or  artificial  states,  as  may  be  exemplified  by 
changes  in  a  ligated  artery  and  by  tlie  development  of  a  collateral  circulation. 
The  mechanisms  by  which  the  adjustments  are  secured  have,  in  consequence 
of  their  physiological  uses,  for  reasons  already  explained,  a  special  fitness  to 
meet  certain  patliological  conditions.  That  this  fitness  should  be  greater  in 
youth  than  in  old  age  is  in  accordance  with  laws  of  life,  indicated  with 


386  ADAPTATION"  IX  PATHOLOGICAL  PEOCESSES 

especial  clearness  by  Minot  in  his  interesting  studies  on  "  Senescence  and 
Rejuvenation/' 

But  these  mechanisms  are  not  equally  well  adapted  to  meet  all  morbid 
changes  in  the  vessels.  Although  Thoma's  interpretation  of  the  fibrous 
thickening  of  the  inner  lining  of  vessels  in  arterio-sclerosis  and  aneurism  as 
compensatory,  or,  as  I  should  prefer  to  say,  adaptive,  is  not  accepted  by  all 
pathologists,  it  seems  to  me  the  best  explanation  in  many  cases.  But  the 
adaptation,  if  it  be  such,  is  here  usually  of  a  verj'  imperfect  nature,  and  it  is 
not  surprising  that  it  should  be  so,  when  one  considers  the  improbability  of 
any  mechanism  developing  under  physiological  conditions  which  sliould  be 
specially  fitted  to  meet  the  particular  morbid  changes  underlying  aneurism 
and  arterio-sclerosis. 

I  shall  not  be  able  to  enter  into  a  consideration  of  the  mechanical  factors 
concerned  in  adaptive  pathological  processes  in  blood  vessels,  although  per- 
haps in  no  other  field  are  to  be  found  more  pertinent  illustrations  of  the 
views  here  advocated  concerning  pathological  adaptations.  The  whole  sub- 
ject has  been  studied  from  the  mechanical  side  most  fully  and  ably  by 
Thoma,  whose  four  beautifully  simple  histo-mechanical  principles  are  at  any 
rate  very  suggestive  and  helpful  working-hypotheses,  even  if  it  should  prove, 
as  seems  to  me  probable,  that  they  are  too  exclusive.  I  shall  call  attention  in 
this  connection  only  to  the  inadequacy  of  the  old  and  still  often  adopted 
explanation  of  the  development  of  a  collateral  circulation.  The  rapidity 
with  which  a  collateral  circulation  may  be  established  after  ligation  of  a 
large  artery,  even  when  the  anastomosing  branches  are  very  small,  is  known 
to  every  surgeon.  This  was  formerly  attributed  to  increase  of  pressure  above 
the  ligature;  but  this  rise  of  pressure  has  been  shown  to  be  too  small  to 
furnish  a  satisfactory  explajiation,  and  Nothnagel  has  demonstrated  tliat 
there  is  little  or  no  change  in  the  calibre  of  arteries  coming  off  close  above 
the  ligature  unless  they  communicate  with  branches  arising  below  the  liga- 
ture. Von  Recklinghausen  several  years  ago  suggested  a  better  explanation. 
The  bed  of  the  capillary  stream  for  the  anastomosing  arteries  is  widened 
by  ligation  of  the  main  artery,  inasmuch  as  the  blood  can  now  flow  with 
little  resistance  from  the  capillaries  of  the  anastomosing  branches  into  those 
of  the  ligated  artery.  The  result  is  increased  rapidity  of  blood-flow  in  the 
anastomosing  vessels.  According  to  one  of  Thoma's  histo-mechanical 
principles,  increased  velocity  of  the  blood-current  results  in  increased  growth 
of  the  vessel-wall  in  superficies — that  is,  in  widening  of  tlie  lumen.  The 
tension  of  the  vessel-wall,  which  is  dopcndont  on  the  diameter  of  the  vessel 
and  the  blood-pressure,  is,  according  to  Thoma,  thus  increased;  and,  accord- 
ing to  another  of  his  principles,  this  greater  tension  results  in  growth  of  the 
vascular  wall  in  thickness.    The  changes  in  the  walls  of  the  anastomosingr 


ADAPTATION"  IN"  PATHOLOGICAL  PROCESSES  387 

vessels  seem  to  me  best  interpreted  as  referable  to  a  genuine  work-hyper- 
trophy, a  conception  which  has  already  been  advanced  by  Ziegler. 

The  pathological  regenerations  constitute  a  large  group  of  adaptive  mor- 
bid processes  of  the  highest  interest.  Their  study  has  become  almost  a 
specialized  department  of  biology,  and  occupies  a  very  prominent  place  in 
the  extensive  literature  of  recent  years  relating  to  experimental  or  physi- 
ological morphology.  It  has  revealed  in  unexpected  ways  the  influence  of 
external  environment  upon  the  activities  of  cells,  as  is  illustrated  in  a  very 
striking  manner  by  Loeb's  studies  of  heteromorphosis. 

Althougli  the  capacity  to  regenerate  lost  parts  must  reside  in  the  inherited 
organization  of  the  participating  cells,  there  are  observations  which  seem  to 
indicate  that  in  the  lower  animals  this  capacity  may  exist  independently  of 
any  opportunity  for  its  exercise  during  any  period  of  the  normal  life  of  the 
individual  or  species  or  their  ancestors,  including  the  period  of  embryonic 
development.  This  is  the  inference  which  has  been  drawn  from  Wolff's 
observation,  that  after  complete  extirpation  of  the  ocular  lens  with  the 
capsular  epithelium  in  the  larval  salamander,  a  new  lens  is  reproduced  from 
the  posterior  epithelium  of  the  iris.  There  are  other  observations  of  similar 
purport.  The  acceptance  of  this  inference,  however,  seems  to  me  to  involve 
such  difficulties  tliat  we  may  reasonably  expect  that  further  investigations 
will  afford  more  satisfactory  explanations  of  these  curious  and  puzzling 
phenomena  of  regeneration.  Of  much  interest  and  significance  are  the  so- 
called  atavistic  regenerations,  where  the  regenerated  part  assumes  characters 
belonging  not  to  the  variety  or  species  in  which  it  occurs,  but  to  some  an- 
cestral or  allied  species.  For  these  and  other  reasons  Driesch  refers  the 
pathological  regenerations  to  what  he  calls  the  secondary  self-regulations, 
by  which  term  he  designates  those  adjustments  of  artificially  induced  dis- 
turbances which  are  brought  about  by  factors  foreign  to  the  normal  develop- 
ment and  life  of  the  individual. 

The  view  advocated  by  Barfurth  seems  to  me  more  probable,  that  the 
pathological  regenerations  depend  upon  cellular  properties  pertaining  to 
the  normal  life  of  the  organism.  This  view  is  supported  by  the  fact  that, 
with  a  few  probably  only  apparent  exceptions,  the  regenerations  conform  to 
the  law  of  specificity  of  cells.  The  pathological  regenerations  occurring 
after  birth  can  be  referred  to  the  retention  in  greater  or  less  degree  of  forma- 
tive powers  possessed  by  the  cells  pre-eminently  in  embryonic  life.  These 
powers  in  general  tend  gradually  to  diminution  or  extinction  as  the  indi- 
vidual grows  older,  although  in  some  cells,  such  as  the  covering  epithelium 
of  the  skin  and  mucous  membranes,  this  loss  of  regenerative  power  with 
advancing  years  is  scarcely  manifest.  Even  after  the  cessation  of  growth 
the  regenerative  capacity  is  not  wholly  in  abeyance  under  physiological  con- 


388  ADAPTATION  IN  PATHOLOGICAL  PROCESSES 

ditions.  Bizzozero  has  studied  and  classified  tlie  various  tissues  of  the  body 
according  to  the  activity  of  their  physiological  regeneration. 

In  general,  the  more  highly  differentiated  and  specialized  a  cell,  the  less 
is  its  capacity  for  regeneration ;  but  we  now  know  that  such  differentiation 
is  attended  with  less  sacrifice  of  its  regenerative  power  than  was  once  sup- 
posed. Even  such  highly  specialized  cells  as  those  of  striped  muscle  are 
capable  of  regeneration.  Indeed,  the  nerve-cells  seem  to  be  the  only  ones 
incapable  of  proliferation,  and  even  this  is  not  certain,  for  there  are  compe- 
tent observers  who  claim  that  these  cells  may  multiply,  although  there  is  no 
evidence  that  in  the  higher  animals  they  can  give  rise  to  functionally  active 
new  nerve-cells.  The  ease  with  which  a  part  of  the  nerve-cell,  namely,  its 
axis-cylinder  process,  can  be  regenerated  is  well  known. 

The  cell-proliferation  in  regeneration  is  attributed  to  the  removal  of  re- 
sistance to  growth  in  consequence  of  the  defect  resulting  from  loss  of  tissue. 
It  has  been  pointed  out«  especially  by  Ziegler  and  by  Ribbert,  that  not  only 
cells  in  the  immediate  neighborhood  of  the  defect  multiply,  but  likewise 
those  at  such  a  distance  that  it  is  difficult  to  suppose  that  the  latter  have  been 
directly  influenced  by  the  loss  of  tension  in  the  tissues  caused  by  the  defect. 
Ziegler  refers  the  proliferation  of  the  distant  cells  to  compensatory  hyper- 
tropliy,  and  Ribl)ert  attributes  it  to  hyperaemia  resulting  from  the  presence 
in  the  defect  of  foreign  materials,  such  as  extravasated  blood,  exudation,  and 
necrotic  tissue. 

We  are  brought  here,  as  we  were  in  the  consideration  of  the  compensatory 
liypertrophies,  to  one  of  the  most  fundamental  and  important  questions  in 
patholog}' — the  causes  of  pathological  cell-growth.  The  interpretation  of 
many  pathological  processes  as  adaptive  or  not,  liinges  often  upon  opinions 
held  concerning  the  underlying  causes  of  cell-proliferation.  The  main  ques- 
tion at  issue  is:  How  far  is  one  willing  to  go  in  attributing  cell-growth  to 
primary  defects  in  the  tissue,  and  interpreting  the  growth  as  for  the  purpose 
of  regeneration  or  filling  up  a  defect?  Differences  of  opinion  upon  this  sub- 
ject are  illustrated  by  the  different  interpretations  of  the  cell-proliferations 
in  acute  and  chronic  inflammations,  some  pathologists  considering  these  to 
be  essentially  regenerative  and  compensatory ;  others  regarding  them,  at  least 
in  large  part,  as  directly  incited  by  inflammatory  irritants  and  not  to  be 
ranked  wholly  with  the  regenerative  processes. 

The  doctrine  of  Virchow  was  long  accepted  without  question,  that  inflam- 
matory cell-growth  is  the  result  of  the  action  of  external  stimuli,  the  so- 
called  inflammatory  irritants,  upon  the  cells,  which  are  thereby  directly 
incited  to  grow  and  nuiltii)ly.  The  attack  upon  this  doctrine  has  been  most 
vigorously  led  by  Weigert,  who  denies  al)solutely  the  power  of  any  external 
agencies  to  stimulate  directly  cells  to  proliferation.     He  considers  that  to 


ADAPTATION  IX  PATHOLOGICAL  PROCESSES  389 

concede  such  a  bioplastic  power  to  external  agents  is  equivalent  to  the  accep- 
tance of  a  kind  of  spontaneous  generation  of  living  matter. 

Weigert's  views  upon  this  subject  have  undoubtedly  had  a  most  fruitful 
influence  upon  pathology.  It  has  been  such  an  influence  as  a  good  working- 
hypothesis,  whether  finally  demonstrated  to  be  true  or  not,  has  often  had  in 
the  development  of  science.  In  putting  to  the  test  of  actual  observation 
Weigert's  hypothesis,  we  have  been  led  to  recognize  the  frequency  and  the 
importance  of  primary  injuries  to  cells  inflicted  by  external  agencies.  Not 
only  various  degenerations  and  necroses  of  entire  cells,  but  more  subtle  and 
partial  damage  of  cytoplasm  and  nucleus  have  been  made  tlie  subject  of 
special  study.  It  has  been  recognized  that  our  older  methods  of  hardening 
tissues  reveal  often  only  very  imperfectly  the  finer  structure  of  cells,  and 
new  and  better  methods  have  been  introduced  which  enable  us  to  detect 
more  delicate  lesions  of  cell-substance  which  formerly  escaped  attention,  as 
is  well  illustrated  in  recent  studies  in  neuropathology.  "Weigert's  postulate 
of  some  primary  injury  to  the  tissues  as  the  immediate  effect  of  mechanical, 
chemical,  and  other  external  agencies,  which  were  formerly  regarded  as  the 
direct  stimuli  of  cell-grovrth  and  multiplication,  has  been  fulfilled  in  many 
instances  where  such  damage  had  previously  been  overlooked  or  unsuspected. 
It  is  his  belief  that  in  cases  where  we  cannot  now  detect  such  primary  injury 
more  thorough  search  and  better  methods  will  enable  us  to  do  so.  One  may, 
of  course,  reasonably  cherish  such  an  expectation ;  but  at  the  same  time  we 
must  recognize  the  fact  that  morbid  cell-proliferations  occur  under  circum- 
stances where  we  cannot  at  present  associate  them  with  any  demonstrable 
injury  to  the  tissues — indeed,  in  some  cases  where  our  insight  into  the  struc- 
ture of  the  part  seems  to  be  so  clear  and  satisfactory  that  one  is  very  reluctant 
to  admit  the  existence  of  an  undetected  damage  to  the  cells. 

Perhaps  the  most  important  modification  of  former  pathological  concep- 
tions, resulting  from  the  belief  that  cell-growth  is  caused  by  primary  defects 
and  injuries  of  tissue,  relates  to  the  chronic  interstitial  inflammations  or 
fibroid  processes.  The  older  view  that  in  these  processes  the  active  and 
essential  feature  of  the  disease  is  the  new  growth  of  connective  tissue,  which 
strangled  the  more  highly  organized  cells  of  the  part,  has  been  replaced  to  a 
large  extent  by  the  opinion  that  the  primary  and  most  important  lesion  is  the 
degeneration,  atrophy,  or  necrosis  of  the  more  specialized  cells,  whose  place 
is  taken  by  the  new  growth  of  interstitial  tissue.  In  many  instances,  as  in 
fibroid  patches  in  the  myocardium,  and  in  many  scleroses  of  the  central 
nervous  system,  this  latter  conception  forms, the  best  and  most  natural  inter- 
pretation of  the  facts.  There  are,  however,  great  difficulties  in  explaining  all 
chronic  interstitial  inflammations  by  this  doctrine,  and  I  must  take  side  with 
those  who  admit  the  occurrence,  for  example,  in  the  kidney  and  in  the  liver, 


390  ADAPTATION  IN  PATHOLOGICAL  PROCESSES 

of  primary  interstitial  inflammations  characterized  by  proliferation  of  the 
connective  tissue  and  endothelial  cells. 

Indeed,  it  seems  to  me  that  Weigert's  formula  is  too  narrow  to  cover  all 
of  the  observed  facts  concerning  cell-proliferation.  Essential  features  of 
the  theory  that  cells  cannot  be  directly  stimulated  to  grow-th  by  external 
agents  were  present  in  Boll's  doctrine  of  border  warfare  between  neighboring 
cells.  Weigert's  presentation  of  this  theory'  is  in  a  far  more  acceptable  shape 
than  tliat  of  Boll.  A  still  more  comprehensive  statement  of  the  general 
theory  is  that  cells  are  incited  to  growth  through  removal  of  ol)stacles  to 
growth  in  consequence  of  some  disturbance  in  the  normal  relations  or 
equilibrium  of  the  cells  with  surrounding  parts.  The  capacity  to  proliferate 
must  be  present  in  the  cells,  but  with  the  cessation  of  growth  this  capacity  is 
rendered  latent  or  potential  by  the  establishment  of  definite  relations  or  an 
equilibrium  between  cells  and  neighboring  parts,  including  under  the  latter 
not  only  adjacent  cells,  but  also  basement-substance,  lymphatics,  blood  vessels, 
tissue-juices,  chemical  substances,  etc.  It  is  evident  that  under  these  cir- 
cumstances in  only  two  ways  can  the  cells  be  incited  to  growi;h,  either  by 
removal  of  resistance  or  obstacles  to  growth,  or  by  an  increase  in  the  forma- 
tive energy  resident  within  the  cell,  and  that  in  either  way  energy  must  be 
used,  whether  it  be  employed  to  remove  obstacles  to  growth,  or  to  increase 
the  proliferative  forces  within  the  cell. 

It  appears  to  me  by  no  means  an  easy  matter  to  decide  in  all  cases  in  which 
of  the  two  ways  mentioned  cell-proliferation  is  brought  about.  Eemoval 
of  obstacles  to  growth,  not  only  in  the  way  indicated  by  Weigert,  but  also  by 
other  disturbances  in  the  neighborhood-relations  of  the  part,  and  very  prob- 
ably by  the  presence  of  definite  chemical  substances,  may  be  the  explanation 
of  all  pathological  cell-growths.  Certainly  it  would  not  be  easy  conclusively 
to  disprove  this  view.  Nevertheless,  I  fail  to  comprehend  tiie  inherent  diffi- 
culties which  some  find  in  admitting  the  possibility  of  forms  of  energy,  act- 
ing from  without,  directly  increasing  the  formative  energy  of  the  cell;  in 
other  words,  directly  stimulating  the  cell  to  growth  and  multiplication.  If 
such  a  possibility  be  admitted,  the  natural  interpretation  of  some  examples 
of  cell-proliferation  is  that  they  are  directly  caused  by  the  action  of  external 
forces,  in  the  sense  advocated  by  Virchow. 

Students  of  the  problems  of  pathological  cell-growth  must  take  into  con- 
sideration not  only  the  facts  of  human  and  allied  pathology,  but  also  those 
which  are  so  rapidly  accumulating  in  the  domain  of  experimental  embry- 
ology and  morphologv',  to  the  importance  of  which  I  have  repeatedly  referred 
in  this  address.  I  would  call  attention  especially  to  the  observations  from 
this  source  as  to  the  influence  of  various  changes  of  environment,  particu- 
larly of  definite  chemical,  thermic,  and  mechanical  changes  in  surrounding 


ADAPTATION  IN  PATHOLOGICAL  PROCESSES  391 

parts,  upon  the  direction  of  movement  and  of  growth  of  cells.  The  use  at 
present  made  of  chemotactic  phenomena  in  explaining  the  direction  of  move- 
ment of  cells  in  human  pathological  processes  is  only  a  very  limited  and  in- 
adequate application  of  these  important  observations  concerning  tactic  and 
tropic  stimuli.  We  shall  probably  come  to  realize  more  and  more  the  opera- 
tion of  these  factors  in  determining  cell-movements  and  cell-growth  in 
human  pathology.  We  already  have  evidence  that  different  kinds  of  leuco- 
cytes not  only  possess  different  specific  functions,  but  also  respond  in  differ- 
ent ways  to  definite  tactic  stimuli.  The  long-standing  problem  of  the  lymph- 
oid cell  in  inflammation  approaches  solution  along  these  lines  of  investiga- 
tion. 

A  burning  question,  and  one  of  perennial  interest,  relating  to  our  sub- 
ject is:  How  far  are  we  justified  in  regarding  acute  inflammation  as  an 
adaptive  or  protective  morbid  process?  There  is  fair  agreement  as  to  the 
essential  facts  of  observation,  but  regarding  their  interpretation  there  are 
wide  differences  of  opinion,  and  when  one  considers  the  complexity  of  the 
process  and  its  still  unsolved  riddles,  it  is  not  hard  to  see  why  this  should 
be  so.  Much  depends  upon  the  point  of  view,  and  in  this  respect  there  can 
be  recognized  a  certain  antagonism  between  the  purely  clinical  and  the  purely 
pathological  and  experimental  views,  an  antagonism,  however,  which  must 
be  reconciled  by  a  fuller  knowledge  of  the  subject. 

It  is  not  likely  that  the  purely  clinical  study  of  inflammation  would  ever 
lead  to  the  idea  that  the  general  tendency  of  this  process  is  advantageous  to 
the  patient.  The  more  severe  and  extensive  the  inflammatory  affection,  the 
more  serious,  as  a  rule,  is  the  condition  of  the  patient.  The  surgeon  sees  his 
wounds  do  well  or  ill  according  to  the  character  and  extent  of  inflammatory 
complication.  Measures  directed  to  the  removal  of  inflammatory  exudation, 
such  as  the  evacuation  of  pus  from  an  abscess  or  an  empyema,  are  the  most 
successful  methods  of  treatment,  and  the  rules  are  embodied  in  ancient 
surgical  maxims.  How  can  one  conceive  of  any  purpose  useful  to  the  patient 
served  by  filling  the  air-cells  of  his  lung  with  pus-cells,  fibrin,  and  red 
corpuscles  in  pneumonia,  or  bathing  the  brain  and  spinal  cord  in  serum  and 
pus  in  meningitis  ?  If  nature  has  no  better  weapons  than  these  to  fight  the 
pneumococcus  or  meningococcus,  it  may  be  asked,  "  What  is  their  use  but 
to  drive  the  devil  out  with  Beelzebub  ?  " 

But  the  pathologist  and  bacteriologist  sees  another  aspect  of  the  picture. 
An  infectious  micro-organism  has  invaded  the  tissues,  where  it  multiplies 
and  where  its  toxic  products  begin  to  work  havoc  with  the  surrounding  cells, 
and  by  their  absorption  to  cause  constitutional  symptoms  and  perhaps 
damage  to  remote  parts.  Is  the  destructive  process  to  go  on  without  any 
defence  on  the  part  of  the  body?    There  are  attracted  to  the  injured  part 


392  ADAPTATIONS^  IN  PATHOLOGICAL  PROCESSES 

an  army  of  leucocytes  from  the  blood  vessels,  and  perhaps  other  cells,  from 
the  neighboring  tissues,  and  it  has  been  conclusively  shown  that  these  cells 
can  pick  up  foreign  particles  and  remove  them,  and  that  they  contain  sub- 
stances capable  of  destroying  many  micro-organisms.  At  the  same  time 
serum  accumulates  in  and  around  the  injured  area,  and  this  may  aid  by  its 
chemical  properties  in  destroying  bacteria,  in  diluting  poisons,  in  flushing 
out  the  part.  Fibrin  may  appear,  and  some  think  that  this  may  serve  in  some 
situations  as  a  protective  covering.  If  these  agencies,  hostile  to  the  invading 
micro-organism,  gain  the  upper  hand,  the  debris  is  cleared  away  by  phago- 
cytes and  other  means,  and  the  surrounding  intact  cells,  which  had  already 
begun  to  multiply,  produce  new  tissue  which  takes  the  place  of  that  which 
had  been  destroyed.  The  victory,  however,  is  not  always  ^svith  the  cells  and 
other  defensive  weapons  of  the  body.  The  struggle  may  be  prolonged,  may 
be  most  unequal,  may  cover  a  large  territory,  and  the  characters  and  extent 
of  the  inflammation  furnish  an  index  of  these  different  phases  of  the  battle. 

Such  in  bald  outlines  are  two  divergent  views  of  inflammation. 

I  da  not  see  how  we  can  fail  to  recognize  in  that  response  to  injury  wliich 
we  call  inflammation,  features  of  adaptation.  Inflammation  may  be  in  some 
cases  the  best  response  to  secure  the  removal  or  destruction  of  injurious 
agents,  but  we  cannot  look  upon  it  as  the  most  perfect  mode  of  protection 
of  the  body  against  invading  micro-organisms.  One  may  inoculate  into 
three  animals,  even  of  the  same  species,  but  possessed  of  different  individual 
resistance,  the  same  quantity  of  the  same  culture  of  a  pathogenic  micro- 
organism and  obtain  sometimes  the  following  results:  The  first  one  will 
present  no  appreciable  inflammatory  reaction  whatever,  and  no  evidences 
of  any  other  disturbance,  and  examination  will  show  that  the  micro-organisms 
have  quickly  disappeared.  The  second  one  will  develop  an  extensive  local 
inflammation  and  survive,  but  after  a  long  illness.  The  third  one  will  offer 
little  resistance  to  the  micro-organism,  which  rapidly  multiplies  without 
causing  marked  inflammation,  invades  the  blood  or  produces  toxaemia,  and 
quickly  destroys  the  life  of  the  animal.  Now,  it  is  evident  that  the  best 
protective  mechanism  is  that  brought  into  action  by  the  first  animal,  but  that 
the  inflammatory  reaction  set  up  in  the  second  one  is  better  than  the  absence 
of  reaction  and  of  other  defences  in  the  third  animal. 

I  can  scarcely  do  more  on  this  occasion  than  to  indicate  some  of  the  points 
of  view  from  which  it  seems  to  me  that  we  can  best  approach  the  study  of 
inflammation  as  an  adaptive  process.  With  inflammation,  as  with  other 
adaptive  processes,  any  useful  purpose  subserved  affords  no  explanation  of 
the  mechanism  of  the  process.  We  should  guard  against  all  ideas  which 
introduce,  even  unconsciously,  the  conception  of  something  in  the  nature  of 
an  intelligent  foresiglit  on  the  part  of  the  participating  cells.    The  response 


ADAPTATION  IN  PATHOLOGICAL  PROCESSES  393 

of  these  cells  in  inflammation  is  a  necessary  and  inevitable  one,  determined 
by  their  innate  properties.  Our  efforts  should  be  directed,  in  the  first  place, 
toward  as  near  an  approach  as  possible  to  a  mechanical  explanation  of  in- 
flammatory processes  by  a  study,  on  the  one  hand,  of  the  properties  and 
mode  of  action  of  the  causes  of  inflammation,  and,  on  the  other  hand,  of  the 
nature  and  source  of  the  cellular  properties  concerned.  We  may  properly 
inquire  whether  these  properties  fit  the  cells  to  counteract  the  effects  of 
injury,  and  if  so,  whence  comes  this  fitness.  Has  the  fitness  those  attributes 
of  relative  perfection  wliich  we  find  in  most  physiological  adaptations?  Is 
the  character  of  the  response  to  injury  in  inflammation  such  as  to  indicate 
that  the  agencies  concerned  have  acquired  through  evolutionary  factors  a 
special  fitness  to  meet  the  pathological  emergencies  ?  Are  all  or  only  a  part 
of  the  manifestation  of  the  inflammatory  processes  adaptive  ? 

It  cannot  be  doubted  that  there  are  innate  properties  of  certain  cells,  called 
into  action  in  inflammation,  such  as  those  manifested  in  the  attraction  of 
leucocytes  and  otlier  cells  by  definite  chemical  substances,  the  capacity  of 
cell- proliferation  from  causes  connected  with  injury,  the  power  of  phago- 
cytosis and  other  bactericidal  properties,  which  may  be  adapted  to  counter- 
act the  effects  of  injurious  agents.  When  these  forces  bring  about  the 
prompt  destruction  or  removal  of  the  injurious  substances  and  the  defect 
is  quickly  repaired,  the  adaptation  is  complete  and  unmistakable.  When, 
however,  the  inflammatory  irritants  and  their  destructive  effects  persist, 
and  the  proliferation  of  cells  and  accumulation  of  inflammatory  products 
become  excessive  and  occupy  large  areas,  the  features  of  adaptation  are  not 
so  easily  recognized.  The  mere  occupation  of  territory  by  inflammatory  prod- 
ucts is  often  a  serious  injury  and  it  can  be  regarded  as  an  adaptive  feature 
only  when  they  fill  some  artificial  defect.  Such  occupation  may  be  in  itself 
enough  to  counteract  any  useful  work  in  which  these  products  may  be  en- 


We  can  reasonably  seek  in  the  relations  of  the  body  to  the  outer  world  an 
explanation  of  the  development  of  certain  properties  of  cells  which  serve  a 
useful  purpose  in  mechanical  and  other  injuries.  These  properties  find 
application  also  in  the  normal  life  of  the  organism.  Their  exercise  in  re- 
sponse to  injury  imparts  to  inflammation  important  adaptive  or  protective 
characteristics,  but  I  fail  to  see  in  this  process  any  such  special  fitness  as 
would  justify  extravagant  statements  which  have  been  made,  to  the  effect  that 
inflammation  ranks  among  the  adaptations  of  living  beings  by  the  side  of 
digestion  and  respiration. 

I  have  endeavored  in  this  address  to  present  certain  general  considera- 
tions concerning  pathological  adaptations.  It  has  been  possible  to  bring 
under  consideration  only  a  small  part  of  an  immense  field,  and  this  very 
28 


394  ADAPTATION  IN"  PATHOLOGICAL  PROCESSES 

inadequately.  We  have  seen  that  in  the  sense  in  which  adaptation  was  de- 
fined we  can  recognize  in  the  results  of  morbid  processes  frequent  and  mani- 
fold evidences  of  adjustment  to  changed  conditions.  These  adjustments 
present  all  degrees  of  fitness.  Some  are  admirably  complete;  more  are 
adequate,  but  far  from  perfect;  many  are  associated  with  such  disorder  and 
failures  that  it  becomes  difiicult  to  detect  the  element  of  adaptation.  The 
teleological  conception  of  a  useful  purpose  in  no  case  affords  an  explanation 
of  the  mechanism  of  an  adaptive  process.  I  have  suggested  that  the  adapta- 
bility of  this  mechanism  to  bring  about  useful  adjustments  has  been  in  large 
part  detennined  by  the  factors  of  organic  evolution,  but  tliat  in  only  rela- 
tively few  cases  can  we  suppose  these  evolutionary  factors  to  have  intervened 
in  behalf  of  morbid  states.  For  the  most  part,  the  agencies  employed  are 
such  as  exist  primarily  for  physiological  uses,  and  while  these  may  be  all 
that  are  required  to  secure  a  good  pathological  adjustment,  often  they  have 
no  special  fitness  for  this  purpose. 

The  healing  power  of  nature  is,  under  the  circumstances  present  in  dis- 
ease, frequently  incomplete  and  imperfect,  and  systems  of  treatment  based 
exclusively  upon  the  idea  that  nature  is  doing  the  best  thing  possible  to 
bring  about  recovery  or  some  suitable  adjustment,  and  should  not  be  inter- 
fered vsdth,  rest  often  upon  an  insecure  foundation.  The  agencies  employed 
by  nature  may  be  all  that  can  be  desired ;  they  may,  however,  be  inadequate, 
even  helpless,  and  their  operation  may  add  to  existing  disorder.  There  is 
ample  scope  for  the  beneficent  work  of  the  physician  and  surgeon. 


HYDROPHOBIA' 

Of  the  many  subjects  suitable  for  the  Eeport  of  the  Chairman  of  this 
Section  I  have  selected  hydrophobia,  on  account  of  the  numerous  and  im- 
portant contributions  to  its  pathology  and  etiology  during  the  past  four  years, 
and  especially  because  the  time  has  come  when  we  can  form  an  intelligent 
estimate  of  the  value  of  the  Pasteurian  inoculations  against  hydrophobia. 
Although  these  inoculations  constitute  the  central  point  about  which  con- 
troversy has  waged,  it  is  not  to  be  forgotten  that  Pasteur's  discoveries  and 
the  investigations  aroused  by  them  have  shed  much  light  in  many  directions 
upon  the  nature  of  one  of  the  most  mysterious  and  fatal  diseases.  Wliat- 
ever  had  been  the  outcome  of  Pasteur's  antirabic  treatment,  his  researches 
upon  hydrophobia  would  still  have  remained  an  important  scientific  con- 
tribution to  our  knowledge  of  the  disease. 

We  are  still  insufficiently  informed  concerning  the  pathological  anatomy 
of  hydrophobia.  I  have  had  opportunity  to  make  post-mortem  examination 
of  three  cases  of  hydrophobia  in  human  beings.  In  one  case  serial  micro- 
scopical sections  were  made  of  the  medulla  oblongata  and  pons  from  the 
second  cervical  nerve  upward.  The  lesions  consisted  in  small  hemorrhages, 
in  accumulations  of  small  round  cells  in  large  numbers,  both  in  the  peri- 
vascular lymph  spaces,  and  in  scattered  foci  in  the  neuroglia  between  the 
nerve  elements,  and  in  thrombi,  composed  of  hyaline  material  and  of  leuco- 
cytes, in  small  blood  vessels.  These  lesions  were  microscopical,  and  their 
extent  and  distribution  could  be  determined  only  by  the  examination  of  a 
large  number  of  sections  from  different  parts.  The  lesions  were  especially 
well  marked  in  and  near  the  nuclei  of  origin  of  the  spinal  accessory,  pneu- 
mogastric  and  glosso-pharj'ngeal  nerves,  and  in  the  motor  nucleus  of  the 
trigeminus.  Cases  have  been  reported  in  which  even  more  extensive  lesions 
than  these  have  been  found;  their  intensity  depending  apparently  in  large 
measure  upon  the  duration  of  the  disease.  While  it  can  not  be  claimed 
that  these  lesions  are  peculiar  to  hydrophobia,  or  by  tliemselves  suffice  for 
its  diagnosis,  it  is  incorrect  to  suppose  that  hydrophobia  is  a  disease  without 
demonstrable  anatomical  lesions  which  bear  a  manifest  relation  to  the 
symptoms  of  the  affection. 

*  Report  of  the  Chairman  of  the  Section  on  Anatomy,  Physiology  and  Pathology, 
before  the  Medical  and  Chirurgical  Faculty,  Baltimore,  April  26,  1889. 
Tr.  M.  &  Chir.  Fac.  Maryland,  Bait,  1889,  162-180. 

395 


396  HYDROPHOBIA 

Far  more  important  than  the  additions  to  our  knowledge  of  the  path- 
ological anatomy  of  rabies  following  Pasteur's  discoveries,  are  the  con- 
tributions to  a  better  comprehension  of  the  causation  of  the  disease.  Before 
Pasteur^s  publications  on  hydrophobia,  dating  from  1881,  about  all  that  we 
knew  of  the  virus  of  rabies  was  tliat  it  was  contained  in  the  salivary  glands 
and  their  secretions,  and  that  infection  often  followed  the  bites  of  rabid 
animals.  We  knew  that  after  characteristic  symptoms  appeared,  the  disease 
was  uniformly  fatal ;  but  we  possessed  no  positive  means  of  diagnosis.  Hence 
it  was  impossible  to  secure  trustworthy  statistics  of  the  mortality  among 
those  bitten  by  rabid  animals ;  for  we  could  not  determine  accurately  how 
many  of  the  animals  were  rabid.  There  obtained  among  a  few  an  unwar- 
rantable scepticism  even  as  to  the  existence  of  such  a  disease  as  hydrophobia. 

We  now  possess  positive  means  of  diagnosis  of  hydrophobia  by  the  inocu- 
lation of  animals,  particularly  of  rabbits ;  so  that  the  last  vestige  of  doubt  as 
to  the  existence  of  the  disease  must  disappear.  We  have  now  valuable  in- 
formation concerning  the  properties  of  the  rabid  virus,  its  distribution  in 
the  infected  body,  the  manner  of  its  transmission,  the  singular  differences 
in  its  action,  according  to  the  mode  and  seat  of  its  inoculation,  and  the 
means  of  producing  immunity  against  its  destructive  action  on  the  body. 

Although  there  is  no  reason  to  doubt  that  the  infectious  agent  of  rabies 
is  a  micro-organism,  no  actual  demonstration  of  this  organism  has  yet  been 
made.  If  fluids  containing  the  rabid  virus  be  filtered  through  substances 
impenetrable  to  particulate  matter,  the  filtrate  is  free  from  infectious 
properties.  In  the  Pathological  Laboratory  of  the  Johns  Hopkins  Univer- 
sity, we  have  had  opportunity  to  study  the  effects  of  the  rabid  virus  upon  a 
series  of  rabbits,  the  original  material  having  been  obtained  from  the  medulla 
oblongata  of  a  man  dead  of  hydrophobia.  We  were  able  abundantly  to  con- 
firm the  statements  of  Pasteur  and  others  as  to  the  behavior  of  these  animals 
when  inoculated  in  succession  with  the  virus  of  rabies.  We  endeavored  by 
cultures  and  by  staining  re-agents  to  demonstrate  some  specific  micro- 
organism ;  but  with  entirely  negative  result.  A  repetition  of  the  methods 
indicated  by  Fol,  failed  to  confirm  his  statements  as  to  the  presence  in  the 
nervous  centres  of  a  demonstrable  species  of  bacteria.  But  while  we  are  not 
acquainted  with  the  specific  organism  causing  hydrophobia,  we  know  many 
of  its  properties. 

The  virus  of  rabies  is  destroyed  by  comparatively  low  temperatures,  ex- 
posure for  one  hour  to  a  temperature  of  50°  C.  {\'i2°  F.)  sufficing  for  this 
purpose.  It  is  killed  in  a  short  time  by  drying,  certainly  within  four  days 
when  exposed  in  thin  layers  capable  of  rapid  desiccation.  It  is  said  to  be 
destroyed  by  ex])osure  to  the  direct  rays  of  the  sun,  even  when  under  condi- 
tions preventing  elevation  of  temperature.    According  to  Babes,  the  virus  is 


HYDROPHOBIA  397 

more  resistant  to  the  action  of  corrosive  sublimate  and  carbolic  acid  than 
most  bacteria ;  but  it  loses  its  infectious  properties  after  exposure  for  three 
hours  to  the  action  of  0.1  per  cent  sublimate,  or  of  1  per  cent  carbolic  acid 
solution.  Galtier  has  pointed  out  a  fact  of  practical  importance,  that  the 
virus  of  rabies  may  be  demonstrated  after  forty-four  days,  and  perhaps 
longer,  in  the  cadavers  of  buried  animals.  An  easy  means  of  preserving 
the  virus  is  to  place  the  brain  or  cord  of  the  infected  animal  in  pure  glycerine, 
which  may  be  diluted  with  water,  and  which  should  be  occasionally  changed. 
In  cases  in  which  persons  are  bitten  by  animals  suspected  of  rabies,  the 
animal  should  be  secured  and  watched,  and  if  it  dies,  the  nervous  centres 
should  be  removed  and  preserved  in  dilute  glycerine  for  subsequent  inocula- 
tion of  rabbits,  whenever  such  inoculation  can  not  be  performed  at  once  by  a 
competent  person. 

It  has  been  ascertained  that  the  certainty  of  infection  with  rabies  depends 
largely  upon  tlie  part  of  the  body  and  the  character  of  the  tissues  into  which 
the  virus  is  inoculated.  The  disease  develops  always  and  with  the  shortest 
period  of  incubation  after  inoculation  of  the  virus  into  the  brain,  or  upon 
its  surface.  Those  who  have  asserted  that  the  same  group  of  symptoms  may 
follow  the  intra-cranial  inoculation  of  substances  other  than  rabid  virus, 
have  fallen  into  serious  error.  Equally  certain  in  the  effects  are  inoculations 
of  the  virus  into  the  eye,  although  here  the  period  of  incubation  is  less 
definite.  Inoculations  into  the  substance  of  nerve  trirnks  appear  to  be 
uniformly  successful  in  rabbits,  but  somewhat  less  certain  in  dogs,  although 
even  in  the  latter  animal  inoculation  into  the  pneumogastric  nerve  does  not 
fail.  Intra-venous  injection  does  not  produce  the  disease  in  ruminants 
unless  large  quantities  of  the  virus  are  used ;  but  it  is  a  ready  means  of  con- 
ferring immunity  upon  these  animals.  The  same  mode  of  injection  suc- 
ceeds often  in  dogs,  and  usually  in  rabbits,  in  produeing  the  disease;  but  it 
may  fail  in  both  classes  of  animals.  Especial  importance  attaches  to  the 
behavior  of  subcutaneous  injections  of  the  virus  of  rabies.  Dogs  often  resist 
infection  from  the  injection  of  considerable  quantities  of  the  most  intense 
virus  into  the  subcutaneous  tissue.  Indeed,  Pasteur  finds  that  the  more 
intense  the  virus,  and  the  larger  the  quantity  injected  subcutaneously,  the 
less  likely  is  the  dog  to  develop  rabies,  and  the  more  certain  is  it  to  acquire 
immunity.  Ferran's  super-intensive  method  of  producing  immunity  in 
human  beings,  is  to  inject  at  once  the  strong  virus  into  the  subcutaneous 
tissue.  Although  he  has  done  this  in  over  400  cases  without  injury,  the 
method  does  not  rest  upon  a  safe  basis  so  far  as  experiments  upon  dogs  are 
concerned ;  for  these  animals  sometimes  contract  the  disease  after  this  mode 
of  inoculation.  Infection  is  more  likely  to  follow  injections  into  the  muscu- 
lar tissue  tlian  into  the  subcutaneous  connective  tissue.     Of  course  the  in- 


398  HYDROPHOBIA 

jection  of  the  virus  into  the  subcutaneous  tissue  by  means  of  a  hypodermic 
syringe  can  not  be  considered  analogous  to  inoculation  by  means  of  bites 
which  wound  the  skin  and  subcutaneous  tissues.  Di  Vestea  and  Zagari  have 
shown  that  while  simple  subcutaneous  injections  are  often  unsuccessful  in 
producing  rabies,  the  application  of  the  virus  to  the  divided  ends  of  nerve 
filaments  in  a  cutaneous  wound  is  generally  efficacious  in  causing  the  disease. 
Although  deep  and  severe  bites  of  rabid  animals  are  the  most  dangerous, 
hydrophobia  may  result  simply  from  a  mad  dog  licking  an  abrasion  or 
scratch.  Intra-peritoneal  injections  of  the  rabid  virus  produce  the  disease 
in  rabbits,  and  guinea-pigs,  if  considerable  quantity  of  the  virus  be  used. 

As  regards  the  distribution  in  the  body  of  the  infectious  material  of  rabies, 
it  has  been  demonstrated  by  Pasteur  that  in  human  beings  or  animals  which 
have  died  of  hydrophobia,  the  virus  is  contained  most  abundantly  in  the 
central  nervous  system,  and  especially  in  the  medulla  oblongata  and  brain. 
It  is  found  also  in  the  nerves  near  their  exit  from  the  brain  and  cord,  but 
less  constantly  and  in  less  amount  in  the  peripheral  nerves.  The  virus  is 
probably  always  present  in  the  salivary  and  lachrymal  glands,  and  some- 
times in  the  pancreas,  but  it  is  usually  absent  from  the  blood,  kidneys,  spleen 
and  liver.  Only  exceptionally  is  it  present  in  the  mammary  glands  and  the 
milk.  It  is  very  rarely  transmitted  to  the  foetus  through  the  placenta.  We 
see,  therefore,  that  the  virus  is  very  unequally  distributed  in  the  body,  and 
that  its  chief  habitat  is  the  central  nervous  system. 

A  point  of  much  interest  is  the  manner  in  which  the  virus  is  conveyed 
from  the  seat  of  inoculation  to  the  central  nervous  system.  The  chief  possi- 
bilities which  present  themselves  are  transmission  by  the  blood-current,  by 
the  lymph-current,  and  along  the  nerve  trunks.  There  is  evidence  that  the 
virus  may  be  conveyed  in  each  of  these  three  ways.  The  production  of  the 
disease  by  intra-venous  and  by  intra-peritoneal  injections  of  the  virus,  speaks 
for  the  first  two  modes  of  transmission.  But  there  are  considerations  which 
favor  the  view  that  the  usual  mode  of  transmission  is  along  the  nerves. 
Inoculations  made  directly  into  nerve  trunks  are  more  certain  to  produce 
rabies  than  either  intra-venous  or  intra-peritoneal  injections,  and  by  the 
first  method  a  smaller  quantity  of  the  virus  suffices.  The  symptoms  of 
rabies,  which  are  chiefly  nervous,  frequently  bear  a  certain  relation  to  the 
seat  of  inoculation  in  the  order  of  their  development.  Thus  when  the  in- 
oculation is  made  into  the  anterior  extremities  or  the  head,  the  first  symp- 
toms are  bull)ar,  whereas,  when  the  inoculation  is  into  tlie  posterior  ex- 
tremities or  tail,  spinal  symptoms,  especially  paralysis  of  the  posterior  ex- 
tremities, appear  first.  No  such  regularity  in  the  sequence  of  symptoms  is 
observed  after  intra-venous  injections.  In  a  large  proportion  of  cases  of 
hydrophobia  in  human  beings,  the  first  symptoms  are  referable  to  disturb- 


HYDROPHOBIA  399 

ances  in  the  nerves  in  or  near  the  injured  part,  and  paraplegia  or  the 
paralytic  form  of  rabies  is  most  likely  to  follow  bites  in  the  lower  extremities. 
By  killing  animals  at  the  proper  period,  it  has  been  ascertained  that  after 
inoculation  in  the  head  or  anterior  part  of  the  body  the  virus  makes  its 
appearance  in  the  medulla  oblongata  sooner  than  in  the  posterior  part  of 
the  spinal  cord,  while  the  reverse  holds  true  when  the  inoculation  is  made  in 
the  tail  or  the  posterior  extremities.  The  virus  propagates  itself  in  steps, 
as  it  were,  along  the  spinal  cord.  Eoux  and  Bardach  have  found  the  virus 
present  in  the  nerves  of  a  bitten  extremity  when  it  has  been  absent  in  the 
corresponding  nerves  of  the  opposite  side;  whereas,  the  reverse  of  this  has 
never  been  observed.  Di  Vestea  and  Zagari  have  succeeded,  in  rabbits,  by 
making  resections  of  the  spinal  cord,  and  keeping  the  divided  ends  separated 
by  a  plug  of  antiseptic  cotton  in  preventing  the  virus  from  extending  from 
one  segment  of  the  cord  to  the  other,  so  that,  after  intra-cranial  inoculations, 
the  upper  segment  contained  the  virus  and  the  lower  did  not,  and  after 
inoculations  into  the  sciatic  nerve,  the  virus  was  prevented  from  passing 
from  the  lower  to  the  upper  segment.  Division  of  a  nerve  trunk  above  the 
point  of  inoculation  may  retard,  but  does  not  prevent  the  development  of 
the  disease,  but  here  there  is  the  possibility  of  the  propagation  of  the  virus 
along  anastomotic  nerve  filaments.  It  must  be  admitted  that  the  facts  and 
experiments  which  have  been  mentioned  speak  strongly  for  the  view  that  the 
virus  passes  along  the  nerves,  although  we  have  no  information  as  to  how 
this  is  accomplished,  and  it  is  not  worth  while  to  consider  the  tlieories  which 
have  been  framed  to  explain  this  interesting  and  curious  phenomenon. 

One  of  the  most  important  discoveries  of  Pasteur  in  this  subject,  is 
that  the  virus  of  rabies  may  undergo  changes  in  certain  of  its  properties  by 
transmission  through  a  series  of  animals  of  the  same  species.  The  principal 
change  is  an  increase  of  virulence,  characterized  by  a  shortened  period  of 
incubation  of  the  disease.  This  change  is  brought  about  by  the  transmission 
of  the  virus  through  a  long  series  of  rabbits,  each  one  being  inoculated 
beneath  the  dura  mater  with  an  emulsion  made  with  the  medulla  oblongata 
of  the  preceding  rabbit  which  has  died  of  hydrophobia.  When  a  rabbit  is 
inoculated  beneath  the  dura  with  the  medulla  of  a  dog  dead  of  rabies,  the 
so-called  rabies  of  the  street  {rage  des  rues),  the  period  of  incubation  of 
the  disease  is  usually  between  15  and  20  days,  and  apparently  never  less 
than  11  days.  By  inoculating  intra-cranially  rabbits  in  series,  beginning 
with  this  first  rabbit,  the  period  of  incubation  is  gradually  reduced  to  seven 
and  finally  to  six  days,  at  which  it  remains  indefinitely.  In  the  series  of 
rabbits  employed  by  Pasteur  for  his  preventive  inoculations,  the  period  of 
seven  days  had  been  reached  before  the  80th  passage,  and  at  the  time  of  the 
178th  passage,  the  period  of  incubation  had  been  for  a  year  6  days  in  at 


400  HYDROPHOBIA 

least  two  out  of  three  of  the  rabbits.  The  virus  from  the  medulla  of  rabbits 
with  this  uniformly  short  period  of  incubation  of  6  or  7  days  is  spoken  of  as 
fixed  virus  {virus  fixe).  The  time  required  for  obtaining  the  fixed  virus 
may  be  very  much  shortened  by  employing  young  rabbits  and  by  inoculating 
several  at  a  time,  selecting  for  successive  inoculations  from  each  group  the 
one  presenting  the  shortest  period  of  incubation.  In  this  way  Hogyes  ob- 
tained the  fixed  virus  in  the  IGth  passage,  about  five  months  after  the  be- 
ginning of  the  successive  inoculations. 

If  the  medulla  of  a  rabbit  which  has  died  of  inoculation  with  the  fixed 
virus  be  preserved  in  a  dry  atmosphere,  its  virulence  progressively  diminishes, 
as  is  indicated  by  the  lengthening  of  the  period  of  incubation.  The  loss  of 
virulence  is  rapid  in  proportion  to  the  temperature  at  which  the  medulla  is 
kept.  The  infectious  properties,  as  a  rule,  disappear  at  the  end  of  a  fort- 
night if  the  temperature  be  from  23°  to  25°  C.  (71.6°— 77°  F.),  and  sooner 
than  this  if  the  medulla  be  of  small  size. 

The  question  arises  whether  these  changes  in  virulence  depend  upon  altera- 
tions in  the  quantity  or  in  the  quality  of  the  infectious  agent.  We  judge  of 
the  degree  of  virulence  mainly  by  the  length  of  the  period  of  incubation  after 
the  intra-cranial  inoculation  of  a  rabbit.  It  has  been  shown  experimentally 
that  this  period  may  be  progressively  lengthened  by  dilution  of  the  virus 
inoculated,  and  this  fact  may  be  put  in  evidence  in  favor  of  a  quantitative 
change  to  explain  varying  degrees  of  virulence.  On  the  other  hand,  fixed 
virus  would  seem  to  difl'er  qualitatively  from  the  virus  of  rabies  of  the  streets, 
for  no  matter  how  prolonged  the  period  of  inoculation  may  be  rendered  by 
dilution  of  the  fixed  virus,  or  in  other  words,  by  diminution  in  the  quantity 
of  the  infectious  agent,  if  this  rabbit  develops  rabies,  its  medulla  always 
contains  the  fixed  virus — that  is,  when  inoculated  intra-cranially  into  an- 
other rabbit,  its  period  of  incubation  is  6  or  7  days,  which  is  shorter  than 
ever  occurs  with  tlie  virus  from  the  rabies  of  the  street.  Pasteur  is  inclined 
to  attribute  the  progressive  loss  in  virulence  of  the  rabbit's  medulla  preserved 
in  a  dry  atmosphere,  to  a  gradual  diminution  in  the  quantity  of  the  infec- 
tious material,  rather  than  to  any  change  in  its  quality. 

It  is  a  significant  fact,  which  should  be  remembered  in  judging  the  results 
of  Pasteur's  treatment,  tliat  there  is  a  period  of  so-called  latent  development 
of  the  virus  in  the  central  nervous  system.  In  rabbits  inoculated  with  the 
fixed  virus,  the  period  of  inoculation  is  six  or  seven  days,  but  as  early  as 
ihe  fourth  day  tlie  virus  has  been  found  in  tlie  medulla  oblongata.  Doubt- 
less, therefore,  in  human  beings  the  virus  is  present  in  the  central  nervous 
system  for  a  period  before  any  characteristic  symptoms  of  rabies  appear, 
so  that  it  may  readily  liaj)pen  that  treatment  is  begun  too  late,  even  when 
undertaken  before  there  are  manifestations  of  tiie  disease.     Careful  obser- 


HYDROPHOBIA  401 

vation  has  shown  that  in  rabbits  this  period  is  not,  strictly  speaking,  a  latent 
one,  but  it  is  accompanied  by  elevation  of  temperature,  increased  frequency 
of  respiration,  slowing  of  the  pulse  rate  and  loss  of  weight,  symptoms  which 
point  to  an  action  of  tlie  rabid  virus  primarily  upon  the  heat  centres  and 
upon  the  vagus. 

It  is  customary  to  divide  rabies  according  to  its  clinical  manifestations 
into  two  forms,  furious  or  convulsive  rabies  and  dumb  or  paralytic  rabies. 
A  third  form,  however,  should  also  be  distinguished — namely,  mixed  rabies, 
which  represents  a  combination  of  convulsive  and  of  paralytic  rabies.  The 
most  common  form  of  rabies  in  human  beings  is  furious  or  convulsive  rabies, 
but  paralytic  rabies  also  occurs  in  man,  especially  after  bites  on  the  lower 
extremities,  and  is  more  common,  according  to  recent  reports,  than  was 
formerly  believed.  In  dogs,  furious  rabies  is  the  predominant  variety, 
whereas,  in  rabbits,  paralytic  rabies  is  the  more  common,  and  in  Pasteur's 
series  it  became  the  sole  form  after  inoculation  with  the  fixed  virus.  A 
careful  study  of  the  symptoms,  however,  renders  less  sharp  the  distinction 
between  furious  and  paralytic  rabies,  for  in  either  form  it  is  often  possible 
to  distinguish  a  stage  of  excitation  and  a  stage  of  paralysis,  but  in  the 
furious  form  the  stage  of  paralysis  is  short  and  may  be  wanting ;  whereas, 
in  the  paralytic  form,  the  stage  of  excitement  is  of  short  duration,  and 
may  be  characterized  only  by  acceleration  of  the  breathing,  elevation  of 
temperature  and  symptoms  referable  to  irritation  of  the  vagus  nerve.  There 
is  probably  no  difference  in  the  quality  of  the  virus  causing  the  two  clinical 
forms  of  hydrophobia,  the  distinction  depending  rather  upon  the  nature  of 
the  animal  infected,  and  the  seat  of  inoculation,  possibly  also  upon  the 
quantity  of  virus  inoculated.  The  only  observation  in  favor  of  differences 
in  the  character  of  the  virus  causing  the  two  varieties  of  rabies  are  those  of 
Helmann,  who  claims  to  have  a  virus  which  will  produce  in  rabbits  invariably 
furious  rabies,  and  another  virus  which  produces  the  customary  paralytic 
rabies,  but  these  observations  have  not  been  confirmed,  are  not  free  from 
objections,  and  are  not  in  harmony  with  the  observations  of  Pasteur  and 
others,  who  find  that  the  virus  of  rabies  of  the  street,  which  is  generally 
furious  in  character,  produces  paralytic  rabies  in  the  rabbit,  and  that  the 
latter  causes  furious  rabies  in  the  dog,  there  being  occasional  exceptions  to 
these  rules.  The  occasional  occurrence  of  paralytic  rabies  in  human  beings 
who  have  not  been  subjected  to  treatment  after  the  bite  of  a  mad  dog,  dis- 
proves the  assertion  of  Peter  that  paralytic  rabies  is  only  rabies  of  the 
laboratory,  and  when  it  has  occurred  in  persons  treated  l)y  Pasteur's  method, 
it  can  be  attributed  only  to  the  anti-rabic  inoculations  and  not  to  the  bite 
of  the  animal,  an  assertion  which,  moreover,  can  be  positively  disproveu  by 
experiment,  as  will  be  explained  subsequently. 


402  HYDROPHOBIA 

There  can  be  no  doubt  whatever  that  it  is  possible  to  render  animals 
immune  against  rabies  both  before  and  after  inoculations  which  would 
otherwise  cause  the  disease.  The  independent  and  careful  experiments  of 
Ernst  in  this  country  are  free  from  all  partisan  bias,  and  have  fully  con- 
firmed the  statements  of  Pasteur  and  others  upon  this  point.  The  methods 
employed  by  Pasteur  for  protective  inoculation  against  hydrophobia  have 
been  so  often  and  so  fully  described  in  medical  and  other  journals,  tliat  it 
is  not  necessary  to  repeat  the  description  on  this  occasion.  The  method  is 
based  upon  the  injection  subcutaneously  (sometimes  in  certain  animals 
into  the  blood)  first  of  attenuated  virus  contained  in  the  medullae,  dried 
for  a  certain  period,  of  rabbits  dead  after  inoculation  with  the  fixed  virus, 
and  then  of  stronger  and  stronger  virus  contained  in  medullae  dried  for 
shorter  periods,  until  strong  or  the  strongest  virus  is  reached.  These  in- 
oculations are  most  effective  in  preventing  the  disease  when  undertaken  soon 
after  the  reception  of  the  poison,  and  with  a  large  quantity  of  virus  and  with 
the  speedy  employment  of  material  containing  the  strongest  virus  (virus 
fixe).  Animals  may  be  rendered  immune  by  a  single  injection  into  the  blood 
or  into  the  subcutaneous  tissue  of  a  large  quantity  of  strong  virus,  whereas 
dogs  which  are  bitten  by  mad  dogs  and  which  do  not  develop  the  disease, 
as  may  happen,  are  not  usually  left  immune,  evidently  because  not  sufficient 
quantity  of  the  virus  has  been  received.  Dogs  which  have  once  been  rendered 
immune  against  rabies  preserve  this  immunity  for  at  least  two  years,  and 
doubtless  for  a  longer  period. 

The  experiments  of  von  Frisch  are  often  quoted  in  opposition  to  the 
validity  of  Pasteur's  conclusions.  Von  Frisch  claimed  that  it  is  impossible 
to  produce  immunity  after  the  virus  of  rabies  has  been  received  in  a  manner 
certain  to  produce  the  disease.  He  urged  that  Pasteur's  experiments  demon- 
strated the  possibility  of  producing  immunity  only  before  and  not  after  the 
reception  of  the  rabid  virus.  In  this  latter  assertion  he  was  in  error.  Von 
Frisch's  failure  to  produce  immunity  after  the  reception  of  the  strong  virus 
was  due  partly  to  his  selection  of  rabbits  for  his  experiments,  and  partly  to 
imperfect  methods  of  preventive  inoculation.  On  account  of  their  extreme 
susceptibility  to  the  rabid  virus,  and  of  the  short  period  of  incubation  after 
intra-cranial  inoculations,  rabbits  are  much  less  suitable  animals  for  these 
experiments  regarding  immunity  than  dogs.  But  even  in  rabbits  immunity 
may  sometimes  be  produced  if  the  preventive  inoculations  be  undertaken 
speedily  after  the  reception  of  the  virus,  and  be  according  to  the  intensive 
method.  Pasteur  and  others  have  shown  that  in  a  large  proportion  of  cases 
the  development  of  rabies  may  be  prevented  in  dogs  even  after  subdural 
injection  of  the  strongest  virus,  if  preventive  inoculations  by  the  intensive 
method  be  begun  not  later  than  the  second  day  after  the  reception  of  the 
poison.     Bardach  succeeded  in  this  way  in  saving  GO  per  cent  of  the  dogs 


HYDROPHOBIA  403 

inoculated  beneath  the  dura  mater.  This  test  is  evidently  the  most  severe 
one  to  which  Pasteur's  preventive  treatment  can  be  subjected,  one  far  more 
severe  than  is  required  to  meet  the  ordinary  channels  of  infection  with  rabies 
in  human  beings,  in  whom  the  period  of  incubation  is  longer  and  the  virus 
is  received  in  less  intense  form  and  in  situations  from  which  infection  is 
slower  and  less  certain.  It  must  be  admitted,  therefore,  that  Pasteur's  treat- 
ment rests  upon  a  satisfactory  experimental  basis,  and  one  which  forms  a 
complete  justification  of  the  application  of  the  treatment  to  human  beings 
bitten  by  rabid  animals. 

We  have  no  positive  knowledge  as  to  the  manner  in  which  immunity  is 
caused  by  the  Pasteurian  vaccination  against  rabies,  any  more  than  we  have 
as  to  the  causation  of  immunity  in  other  diseases.  Pasteur  is  inclined  to 
attribute  the  immunity  to  the  action  of  some  substance,  which  he  calls 
"  matiere  vaccinale"  contained  in  the  inoculated  material,  but  not  identical 
with  the  micro-organism  causing  rabies.  That  immunity  against  infectious 
diseases  may  be  secured  by  the  injection  of  chemical  substances  produced 
by  the  growth  of  specific  bacteria,  was  demonstrated  by  Salmon  and  Smith 
in  the  case  of  hog  cholera,  and  has  been  since  demonstrated  by  Eoux  and 
Chamberland  for  malignant  oedema,  and  by  Wooldridge  for  anthrax.  It 
has  not  yet  been  found  possible  to  prove  the  correctness  of  Pasteur's  sup- 
position in  the  case  of  rabies,  and  although  there  are  arguments  in  its  favor, 
it  is  hardly  worth  while  for  us  to  consider  further  a  question  at  present  in 
so  hypothetical  a  state. 

Encouraged  by  the  results  of  his  experiments  upon  animals,  Pasteur,  in 
July,  1885,  first  applied  to  a  human  being  his  method  of  preventing  hydro- 
probia  by  successive  injections  of  the  virus  contained  in  the  rabbit's  medulla 
subjected  to  drying  for  different  periods,  the  medulla  being  taken  from  rab- 
bits which  had  died  after  inoculation  with  the  fixed  virus. 

During  the  years  1886,  1887,  and  the  first  half  of  1888,  there  have  been 
treated  under  Pasteur's  super Wsion,  either  by  the  simple  or  by  the  intensive 
method  of  vaccination,  5374  persons  who  have  been  bitten  by  animals 
either  proven  or  suspected  to  be  rabid.  The  mortality  from  hydrophobia, 
including  even  the  cases  which  developed  within  a  day  after  the  cessation  of 
treatment,  was  for  1886  1.3-1  per  cent;  for  1887,  1.12  per  cent;  for  the  first 
half  of  1888,  0.77  per  cent.  If  the  fatal  cases  which  developed  within  a  fort- 
night after  the  end  of  treatment,  and  in  which  there  is  reason  to  believe  that 
the  inception  of  treatment  was  too  late,  be  excluded,  the  mortality  for  1886 
falls  to  0.93  per  cent;  for  1887,  to  0.67  per  cent;  and  for  the  first  half  of 
1888,  to  0.55  per  cent.     From  May  1,  1888,  to  May  1,  1889,'  there  were 

'  I  have  endeavored  to  bring  the  statistics  of  this  paper  up  to  the  date  of  its 
publication  (July,  1889),  and  have  therefore  added  certain  statistics  which  have 
appeared  since  the  time  the  paper  was  read  in  April,  1889. 


404  HYDROPHOBIA 

treated  at  the  Pasteur  Institute,  in  Paris,  1673  persons  bitten  by  dogs, 
either  rabid  or  suspected  to  be  rabid.  Of  these  6  died  during  treatment,  4 
in  less  than  a  fortnight  after  treatment,  and  3  died  later  than  a  fortnight 
following  the  cessation  of  treatment.  Only  the  last  3  cases,  therefore,  are 
to  be  counted  as  failures.  If  all  the  deaths,  both  during  and  after  treatment, 
be  included,  which  would  be  illogical,  the  mortality  equals  0.78  per  cent; 
if  only  the  deatlis  after  treatment  be  reckoned,  the  mortality  becomes  0.42 
per  cent;  and  if  only  those  occurring  more  than  a  fortnight  after  the  end 
of  treatment  be  estimated,  the  death-rate  sinks  to  0.18  per  cent.  This 
mortality  may  be  somewhat  increased  by  subsequent  deaths,  as  sufficient 
time  has  not  elapsed  for  full  completion  of  the  returns.  Pasteur,  in  a  recent 
letter  to  Sir  H.  Eoscoe,  says  that  up  to  the  end  of  June,  1889,  over  7000 
persons  have  been  treated  in  his  laborator}-,  and  that  the  general  mortality 
applicable  to  the  whole  number  of  the  operations  was  1  per  cent. 

Doubtless  a  considerable  numiber  of  cases  are  included  in  the  foregoing 
statistics  of  persons  subjected  to  treatment  who  have  not  been  bitten  by 
animals  actually  rabid.  How  large  is  this  number,  it  is  impossible  to  say ; 
but  even  if  ample  allowance  be  made  for  tliis  class  of  cases,  the  results  of  tlie 
treatment  can  hardly  be  interpreted  otherwise  than  in  favor  of  its  efficacy. 

It  is  possible,  however,  to  select  from  the  reports  only  those  cases  in  which 
the  animal  inflicting  the  injury  has  been  actually  proven  to  be  rabid.  This 
proof  is  the  most  exact  which  can  be  furnished,  and  consists  in  the  results 
of  the  inoculation  of  animals  with  the  brain  or  cord  of  the  animal,  or  in  the 
development  of  hydrophobia  in  persons  or  animals  bitten  at  the  same  time 
as  those  treated,  Pasteur's  statistics,  which  are  published  monthly,  are 
arranged  in  tables  which  embrace:  A — Persons  bitten  by  animals  proven 
to  be  rabid :  B — Cases  in  which  the  existence  of  rabies  in  the  animal  is  cer- 
tified by  a  veterinarian :  C — Cases  in  which  there  is  reason  to  suspect  rabies 
in  the  animal,  although  the  evidence  furnislied  in  the  foregoing  classes  was 
not  obtained. 

If  the  cases  be  analyzed  according  to  this  classification,  we  obtain  the 
following  results:  Since  the  beginning  of  his  operations  in  July,  1885,  up 
to  the  end  of  the  first  half  of  1889,  there  have  been  treated  under  Pasteur's 
supervision  6950  patients.  There  were  bitten  by  animals  suspected,  but  not 
proven  to  be  mad,  1187,  of  whom  12,  or  1.01  per  cent,  died;  by  animals  pro- 
nounced rabid  by  veterinarians,  4686  persons,  of  whom  44,  or  0.94  per  cent, 
died;  and  by  animals  proven  experimentally  to  be  rabid,  1077  persons,  of 
whom  15,  or  1.39  per  cent,  died.  The  similarity  of  the  results  in  the  three 
classes  shows  that  the  second  and  third  groups  must  contain  a  large  number 
of  cases  in  which  the  wounds  were  inflicted  by  rabid  animals.  If  we  exclude 
from  the  preceding  statistics  those  who  began  treatment  a  fortnight  or  more 


HYDROPHOBIA  405 

after  being  bitten,  we  find  the  death-rate  in  Class  C  to  be  5,  or  0.43  per  cent ; 
in  Class  B,  31,  or  0.66  per  cent,  and  in  Class  A,  11,  or  1.2  per  cent. 

The  most  convincing  presentation  of  the  case  is  to  select  the  results  of 
treatment  in  persons  bitten  on  the  head  and  face  by  animals  proven  to  be 
rabid.  In  all  statistics  purporting  to  give  the  mortality  from  the  bites  of 
rabid  animals,  by  far  the  largest  death-rate  is  afforded  by  the  bites  on  the 
head  and  face.  I  have  collected  from  Pasteur's  reports  for  1887  and  1888, 
tliose  bitten  on  the  head  and  face  by  animals  proven  experimentally  to  be 
rabid.  There  were  73  cases,  with  4  deaths  from  rabies  during  treatment, 
and  3  following  treatment.  Of  the  latter,  one  was  seized  three  days  after 
the  end  of  treatment,  and  it  is  therefore  reasonable  to  suppose  that  in  this 
case  the  treatment  was  begun  too  late.  If  this  case  and  those  dying  during 
treatment  be  excluded,  there  remain  67  cases  bitten  on  the  head  or  face  by 
animals  proven  to  be  rabid,  with  2  deaths,  a  mortality  of  3  per  cent.  I  was 
not  able  to  obtain  the  data  for  an  analysis  of  all  of  the  cases  in  this  group 
since  the  beginning  of  Pasteur's  treatment ;  but  after  collecting  these  cases, 
I  have  met  the  statement  that  the  total  number  of  persons  bitten  on  the  face 
and  neck  by  animals  proven  to  be  rabid  is  540;  of  whom  21  died,  leaving 
a  mortality  of  3.89  per  cent;  but  how  many  of  these  are  fairly  attributable 
to  failure  of  the  treatment  does  not  appear.  These  cases  undoubtedly 
belong  to  both  Class  A  and  Class  B. 

Unless  it  can  be  shown  that  the  mortality  following  the  bites  of  rabid 
animals  is  as  small  as  that  derived  from  the  foregoing  statistics,  no  other 
conclusion  can  be  drawn  than  that  Pasteur's  treatment  is  efficacious;  for 
we  can  dismiss  as  unworthy  of  consideration  all  attempts  to  cast  doubt  upon 
the  truthfulness  of  the  statistics  published  by  Pasteur.  Not^^'ithstanding 
the  out-cry  of  those  who  assert  that  nothing  can  be  proven  in  medicine  by 
statistics,  it  is  apparent  that  Pasteur  could  have  proceeded  in  no  other  way 
than  he  has  done,  in  order  to  demonstrate  the  value  of  his  treatment,  and 
that  the  statistical  method  is  the  only  one  applicable  to  this  demonstration, 
although  we  are  to  keep  in  mind  all  possibilities  of  error  belonging  to  the 
method. 

There  are  various  careful  collections  of  statistics  which  show  that  a  con- 
servative estimate  of  the  average  mortality  of  persons  bitten  by  rabid  animals 
is  about  15  per  cent  (Lablanc,  Dujardin-Beaumetz,  Horsley).  The  results 
of  different  statistics  on  this  point  vary  widely,  as  is  to  be  expected  from 
the  fact  that  they  include  generally  in  large  but  variable  numbers  bites  from 
animals  not  proven  to  be  rabid.  On  this  point  Pasteur's  statistics  have  the 
merit  of  greater  accuracy.  It  is  logical  to  suppose  that  the  statistics  with 
large  mortality  include  a  greater  proportion  of  bites  from  actually  rabid 
animals  than  those  with  small  mortality. 


406  HYDROPHOBIA 

All  agree  that  bites  on  the  head  and  face  by  rabid  animals  furnish  the 
highest  mortality.  This  is  given  by  Brouardel  as  88  per  cent.  If  we  place 
it  at  60  to  80  per  cent,  we  are  likely  certainly  not  to  exaggerate  the  mortality. 

If  now  we  contrast  with  these  moderate  estimates  of  the  mortality  follow- 
ing the  bites  of  rabid  animals,  the  results  obtained  by  Pasteur's  method  of 
treatment,  there  is  left  no  room  for  doubt  that  this  treatment  has  been 
proven  to  be  efficacious,  and  has  saved  already  hundreds  of  lives.  I  call 
attention  especially  to  the  convincing  character  of  the  results  in  persons 
bitten  on  the  head  and  face  by  animals  proven  to  be  rabid. 

The  Pasteurian  treatment,  as  is  apparent  from  the  preceding  statistics, 
has  a  certain  number  of  failures  to  record.  It  is  not  therefore  unfailing, 
although  if  we  compare  its  results  with  those  obtained  by  methods  of  medical 
treatment  in  various  diseases,  it  takes  a  very  high  rank,  perhaps  second  only 
to  vaccination  in  small-pox.  The  death  from  hydrophobia  in  two  instances 
of  persons  over  two  years  after  treatment,  casts  a  certain  shadow  upon  the 
results,  but  can  not  invalidate  the  general  conclusions  as  to  the  efficacy  of 
the  treatment. 

It  is  most  encouraging  that  the  results  of  the  treatment  have  improved 
with  each  successive  year  of  its  application.  This  is  attributable  to  improve- 
ments in  the  methods,  and  is  even  more  strikingly  illustrated  in  the  statistics 
of  some  others  than  in  those  of  Pasteur,  but  I  have  preferred  in  this  article 
to  consider  only  the  results  obtained  under  Pasteur's  immediate  supervision. 
Essentially  similar  results,  however,  have  been  obtained  in  various  places, 
chiefly  in  Russia,  Italy  and  South  America.  The  principal  improvement  in 
the  method,  as  first  applied  by  Pasteur,  is  in  the  elaboration  of  the  so-called 
intensive  method  of  preventive  inoculation  which  is  applicable  to  severe 
cases,  especially  to  those  bitten  in  the  head  or  face  and  by  wolves.  In  some 
anti-rabic  institutes  the  intensive  method  has  entirely  superseded  the  simple 
method. 

It  is  a  sufficient  answer  to  the  assertion  that  has  been  made  that  Pasteur's 
intensive  inoculations  are  dangerous,  in  that  they  may  actually  produce  tlie 
disease,  that  the  mortality  from  rabies  is  strikingly  smaller  after  the  appli- 
cation of  the  intensive  method  than  after  the  simple  treatment.  There  is, 
furthermore,  a  method  of  demonstrating  experimentally  that  those  who 
may  die  from  rabies  after  preventive  inoculations  have  not  contracted  the 
disease  by  means  of  the  inoculations.  These  inoculations  are  made  with  the 
fixed  virus,  of  which  the  period  of  incubation  in  rabbits  after  sub-dural 
injection  is  six  or  seven  days ;  whereas  those  treated  were  bitten  by  animals 
affected  with  rabies  of  the  street,  the  virus  of  which  after  sub-dural  inocula- 
tion of  rabbits  has  a  period  of  incubation  of  fifteen  to  twenty  days.  As  has 
been  already  mentioned,  even  if  the  period  of  incubation  of  the  fixed  virus 


HYDROPHOBIA  407 

be  lengthened  by  dilution  or  attenuation  of  the  virus,  or  if  it  be  used  to  kill 
another  animal  as  a  dog,  the  virus  as  obtained  from  the  brain  or  cord  of 
the  latter  animal  is  still  fixed  virus,  and  will  destroy  rabbits  with  a  period 
of  incubation  of  six  or  seven  days.  Now,  in  all  instances  in  which  the  brain 
or  cord  of  a  human  being  dying  of  rabies  after  the  Pasteurian  treatment  has 
been  used  to  inoculate  rabbits,  it  has  been  found  to  contain  virus  with  the 
period  of  incubation  of  rabies  of  the  street,  and  not  fixed  virus,  or  in  other 
words,  not  the  kind  of  virus  which  was  used  for  the  preventive  inoculation. 
We  are  not  to  forget  that  the  measures  which  are  of  first  importance  in 
preventing  hydrophobia  must  be  directed  against  the  development  and  ex- 
tension of  the  disease  in  dogs ;  for  if  canine  rabies  could  be  eradicated,  there 
need  be  no  fear  of  the  disease,  at  least  in  this  country  and  in  eastern  Europe. 
These  measures  consist  in  good  dog  laws,  and  their  efficient  application,  A 
proper  tax-rate  upon  dogs,  their  muzzling,  and  the  destruction  of  stray  and 
ownerless  dogs,  are  the  principal  measures.  It  may  be  well  also  to  enforce 
quarantine  measures  against  dogs  imported  from  countries  where  rabies  is 
prevalent.  In  most  parts  of  Germany  these  preventive  measures  are 
thoroughly  enforced,  and  the  result  is  an  almost  total  disappearance  of 
rabies ;  whereas  in  France  similar  measures  are  not  carried  out,  and  rabies  is 
consequently  alarmingly  prevalent.  I  do  not  know  of  any  data  which  enable 
us  to  determine  the  extent  of  prevalence  of  rabies  in  this  country ;  but  so  far 
as  can  be  judged  by  general  impressions,  it  does  not  seem  to  be  common  with 
us.  Its  occurrence  at  all,  however,  is  sufficient  reason  for  the  enforcement  of 
those  measures  which  have  been  found  most  efficient  in  its  prevention. 


CIRRHOSIS  HEPATIS  ANTHRACOTICA/ 

I  have  placed  under  the  microscopes  sections  of  a  liver  showing  a  peculiar 
form  of  cirrhosis  associated  with  the  deposition  of  coal  pigment.  The 
specimen  of  liver  together  with  portions  of  other  organs  were  sent  to  me 
recently  by  Dr.  Unger,  of  Mercersburg,  Pa.,  for  microscopical  diagnosis. 
All  that  I  have  been  able  to  learn  of  the  history  of  the  man  from  whom  the 
specimens  w^ere  obtained  is  as  follows :  He  was  a  German,  about  70  years 
of  age,  who  had  lived  for  many  years  as  a  farmer  in  the  neighborhood  of 
Mercersburg,  Pa.  He  is  said  to  have  worked  as  a  weaver  in  Germany,  but 
nothing  more  definite  concerning  his  occupation  or  life  in  that  country  could 
be  learned.  The  place  where  he  lived  in  Pennsylvania  is  not  particularly 
smoky.  His  health  was  good  until  about  two  years  ago  when  he  began  to 
suffer  from  vomiting,  loss  of  api>etite  and  severe  pain  in  the  abdomen. 
Accumulation  of  fluid  in  the  peritoneal  cavity  necessitated  repeated  tappings 
by  which  serous  fluid  was  withdrawn.  The  patient  grew  very  weak  and 
emaciated. 

The  autopsy  was  made  by  Dr.  Unger,  and  on  account  of  special  external 
circumstances  was  necessarily  hasty  and  incomplete.  Only  the  abdominal 
organs  were  examined  and  Dr.  linger  as  regards  these,  was  chiefly  interested 
in  the  character  of  the  new  growth  which  was  found.  The  peritoneum  was 
found  much  thickened  and  presented  many  nodular  masses,  mostly  of  small 
size.  The  omentum  was  thickened  and  retracted  into  a  hard,  nodulated, 
cord-like  mass.  The  mesentery  was  likewise  thickened  and  retracted.  A 
number  of  small,  hard,  whitish,  circumscribed  nodules  were  found  in  the 
superficial  part  of  the  liver.  Pieces  of  the  liver,  omentum  and  peritoneum 
were  sent  to  me  for  examination.  Sections  of  the  nodular  tumors  showed 
them  to  be  carcinomata,  presenting  a  fibrous  stroma  rich  in  cells  and  irregu- 
lar alveoli  filled  witli  polyhedrical  and  cul)oidal  cells.  Tbe  primary  origin 
of  the  cancer  was  not  det-ermiued,  although  doubtless  a  more  complete 
autopsy  would  have  revealed  it. 

The  most  interesting  feature  of  the  case,  however,  is  the  condition  of  the 
liver.  Of  this  organ  several  pieces  hardened  in  alcohol  were  sent.  On  the 
cut  surface  as  well  as  through  the  capsule  of  the  liver  can  be  seen  with  the 

*  Delivered  before  the  Johns  Hopkins  Hospital  Medical  Society,  December  15, 
1890. 

Johns  Hopkins  Hosp.  Bull.,  Bait.,  1891,  II,  32-33. 

408 


CIRRHOSIS  HEPATIS  ANTHRACOTICA  409 

naked  eye  numerous  small  black  specks  and  small  streaks.  These  little  black 
lines  and  dots  are  present  everywhere  throughout  the  liver  scattered  irregu- 
larly at  intervals  not  more  than  0.5  to  1  mm.  apart.  They  are  irregular  in 
size  and  shape.  They  are  not  present  in  the  cancerous  nodules  nor  more 
abundant  in  their  neighborhood  than  elsewhere.  Some  of  the  pieces  of  liver 
which  were  sent  do  not  contain  any  cancerous  nodules.  Around  many  of  the 
black  specks  the  tissue  has  a  grayish  color.  The  prevailing  color  of  the  liver 
substance  between  the  black  deposit  is  yellowish  brown. 

On  microscopical  sections  the  little  black  spots  and  streaks,  sometimes 
lying  in  a  grayish  tissue,  sometimes  in  the  yellowish  brown  liver  substance, 
can  be  seen  distinctly  with  the  naked  eye.  By  microscopical  examination  the 
block  foci  are  seen  to  be  due  to  the  deposit  of  black  granules  in  all  respects 
identical  with  the  coal  pigment  found  in  the  lungs.  The  granules  are  of  a 
pure  black  color,  vary  in  size  from  granules  about  one-quarter  the  diameter 
of  a  red  blood  corpuscle  to  very  minute  granules,  occur  sometimes  in  large 
conglomerate  masses  evidently  composed  of  a  close  aggregation  of  granules, 
and  are  sometimes  quite  regularly  round,  but  may  be  slightly  irregular  and 
angular  in  shape.  They  occur  both  free  and  enclosed  in  cells.  They  remain 
unchanged  when  the  sections  are  treated  with  concentrated  sulphuric  acid 
as  well  as  with  boiling  glacial  acetic  acid,  hydrochloric  acid,  nitric  acid, 
aqua  ammoniac  or  concentrated  liquor  potassae.  Compared  with  the  coal 
pigment  found  so  often  in  the  lungs  and  bronchial  glands  absolutely  no 
points  of  difference  can  be  detected  and  I  have  therefore  no  hesitation  in 
saying  that  they  are  coal  particles. 

The  particles  of  coal  pigment  are  not  distributed  uniformly  throughout 
the  liver  as  is  the  case  with  malarial  pigment  but  occur  in  scattered  areas. 
There  are  in  some  places  small  deposits  of  the  pigment  between  unchanged 
liver  cells.  These  deposits  between  liver  cells  are  generally  within  round 
or  irregular  cells  lying  against  the  capillary  walls  and  sometimes  appear  to  be 
contained  in  Kupfer's  cells.  The  black  pigment  is  never  within  the  hepatic 
cells.  As  a  rule  the  pigment  lies  within  bands  and  nodules  of  dense  fibrous 
tissue,  and  it  is  the  character  of  these  fibrous  areas  and  the  relation  to  them 
of  the  coal  pigment  that  make  the  unusual  feature  of  the  case. 

These  fibrous  areas  differ  in  distribution  and  in  appearance  from  the 
formation  of  fibrous  tissue  in  ordinary  hepatic  cirrhosis.  The  fibrous  areas 
are  sharply  circumscribed.  They  never  completely  surround  a  lobule.  They 
occur  most  frequently  in  the  interlobular  tissue,  but  they  are  also  often 
formed  around  the  central  vein  as  well  as  at  any  point  in  the  interior  of  the 
lobule.  They  vary  in  size.  Some  are  not  larger  than  a  group  of  five  or 
six  liver  cells,  others  occupy  nearly  the  entire  field  of  the  miscroscope  with 

29 


410  CIRRHOSIS  HEPATIS  ANTHRACOTICA 

Zeiss  objective  A,  ocular  3.  The  majority  are  much  smaller  than  this  latter 
dimension,  averaging  about  one-sixth  to  one-eighth  the  diameter  of  a  liver 
lobule.  Five  to  eight  such  nodules  can  usually  be  seen  in  each  field  of  the 
microscope  with  Zeiss  A,  ocular  3.  The  shape  of  the  fibrous  patches  varies, 
but  there  is  a  general  tendency  to  assume  a  round  or  oval  shape.  Many  of 
the  patches,  however,  are  long  and  narrow  following  the  course  of  the  inter- 
lobular vessels  or  the  rows  of  liver  cells.  The  fibrous  areas  are  in  general 
composed  of  dense  sclerotic  fibrous  tissue  poor  in  cells,  these  cells  being 
chiefly  elongated  connective  tissue  cells  closely  applied  to  the  fibres  and 
cells  containing  black  pigment.  Some  of  the  areas,  especially  the  smaller 
intralobular  ones  are  composed  of  a  hyaline  indistinctly  fibrillated  material 
poor  in  cells.  In  the  interlobular  fibroid  formations  can  be  seen  very  much 
compressed  interlobular  veins,  branches  of  the  hepatic  artery  with  thickened 
walls  resulting  from  an  obliterating  endarteritis  leading  in  some  instances  to 
complete  obliteration  of  the  vessel,  and  bile  ducts.  The  bile  ducts  are  few 
and  there  appear  to  be  no  so-called  newly  formed  bile  ducts  so  often  observed 
in  ordinary  cirrhosis.  All  of  the  fibroid  formations,  whether  intralobular 
or  interlobular,  contain  in  large  amount  black  coal  pigment,  both  free  and 
in  roimd  oval,  and  elongated,  sometimes  branching  cells.  With  the  excep- 
tion of  the  comparatively  few  small  deposits  seen  between  normal  liver  cells, 
the  coal  deposits  are  found  only  in  the  fibroid  masses  and  the  growths  of 
fibrous  tissue  do  not  occur  except  in  association  with,  the  pigmentar}-  deposits. 
There  can  be  seen  on  careful  examination  unmistakable  evidences  that  the 
new  growth  tissue  is  referable  directly  to  the  deposition  of  coal  pigment. 
Where  the  pigment  is  surrounded  by  normal  liver  cells,  it  is  present  only  in 
comparative  small  amount.  There  are  places  where  a  clump  of  the  pigment 
is  surrounded  by  two  or  three  homogeneous  liver  cells  devoid  of  nuclei  or  by 
a  little  hyaline  or  finely  granular  material  replacing  two  or  three  imme- 
diately adjacent  liver  cells,  and  places  where  a  small  area  of  nearly  homo- 
geneous basement  substance  containing  a  mass  of  coal  pigment  has  taken 
the  place  of  not  more  than  five  or  six  liver  cells  in  the  interior  of  a  lobule 
and  all  transitions  exist  between  these  small  areas  and  the  larger  ones.  The 
appearances  indicate  that  small  deposits  of  the  coal  pigment  do  not  injure 
the  surrounding  liver  cells,  that  larger  deposits  lead  to  a  death  of  the  immedi- 
ately adjacent  liver  cells,  and  as  a  result  of  this  loss  of  liver  cells,  a  new 
growth  of  dense  fibrous  tissue  is  developed. 

The  histological  picture  is  quite  different  from  that  of  ordinary  hepatic 
cirrhosis.  Instead  of  interlacing  bands  of  connective  tissue  more  or  less 
completely  surrounding  lobules  or  groups  of  lobules,  we  have  in  the  present 
instance  sharply  circumscribed,  round,  oval  and  elongated  discrete  areas  of 


CIRRHOSIS  HEPATIS  ANTHRACOTICA  411 

sclerotic,  at  times  nearly  homogeneous,  fibrous  tissue,  containing  such  masses 
of  coal  pigment  as  to  appear  in  places  almost  uniformly  black.  Different  as 
are  the  appearances  from  ordinary  cirrhosis,  there  is  manifestly  a  close 
analogy  between  the  changes  in  this  liver  and  those  occurring  in  indurative 
anthracosis  of  the  lungs.  In  both  is  found  the  same  formation  of  circum- 
scribed bands  and  nodules  of  dense  fibrous  tissue,  colored  black,  with  coal 
pigment. 

This  anthracosis  of  the  liver  has  no  relation  to  the  presence  of  the  secon- 
dary cancerous  nodules  in  the  liver  which  are- entirely  free  from  pigment. 

Besides  the  changes  mentioned  there  is  no  other  lesion  of  the  liver  save 
a  considerable  bile  pigmentation  of  the  liver  cells. 

The  presence  of  a  small  amount  of  coal  pigment  in  the  liver  is  not  par- 
ticularly uncommon.  Instances  have  been  reported  by  Arnold,  Soyka,  Wei- 
gert  and  others.  We  owe  to  Weigert  and  to  Arnold  especially  the  establish- 
ment of  the  especial  conditions  leading  to  this  occurrence.  Whereas  under 
ordinary  conditions  the  bronchial  lymphatic  glands  form  an  effectual  fil- 
ter against  the  entrance  into  the  blood  of  coal  pigment  inspired  into  the 
lung,  Weigert  has  shown  that  adhesions  and  destructive  inflammations  may 
open  the  way  for  the  passage  of  this  pigment  from  the  glands  directly  into 
adjacent  blood  vessels,  and  it  is  probable  that  similar  alterations  in  the  lungs 
may  lead  to  the  same  result.  Arnold  has  pointed  out  the  frequent  associa- 
tion of  emphysema  of  the  lungs  with  the  presence  of  coal  pigment  in  the 
spleen,  liver  and  elsewhere.  It  is  unfortimate  that  in  the  present  case  we 
have  no  clue  as  to  the  condition  of  the  lungs  or  of  the  bronchial  glands,  but 
we  can  hardly  be  mistaken  in  assuming  that  some  abnormal  condition 
existed  which  permitted  an  unusually  free  entrance  into  the  circulating 
blood  of  coal  pigment  from  these  situations.  I  have  repeatedly  had  the 
opportunity  of  confirming  the  observations  both  of  Weigert  and  of  Arnold, 
but  I  have  never  before  seen  a  liver  containing  such  a  large  amount  of  coal 
pigment  as  the  present  one,  which  is  speckled  everywhere  with  black  dots  and 
streaks.  Ordinarily  the  presence  of  coal  pigment  in  the  liver  is  not  asso- 
ciated with  any  important  lesions  referable  to  the  deposition  of  the  pigment. 
Careful  examination,  however,  will  often  reveal  atrophied  liver  cells  and  a 
small  quantity  of  dense  fibrous  tissue  poor  in  cells  aroimd  coal  deposits  of 
considerable  size,  but  as  far  as  I  can  learn,  this  is  the  first  instance  recorded 
of  a  peculiar  form  of  wide-spread  cirrhosis  of  the  liver  dependent  upon  the 
presence  of  coal  pigment,  and  I  propose  to  designate  the  condition  cirrhosis 
hepatis  anthrocotica. 

From  the  description  already  given,  it  is  clear  that  the  primary  change 
leading  to  the  cirrhosis  is  the  atrophy  and  death  of  liver  cells.  Whether  we 
are  to  attribute  this  cell  death  to  a  mechanical  or  to  a  chemical  action  of 


412  CIRRHOSIS  HEPATIS  ANTHRACOTICA 

the  pigment  deposits  cannot  be  positively  determined,  but  the  former  seems 
the  more  probable  view.  Still,  as  pointed  out  by  Weigert,  the  coal  particles 
inhaled  may  carry  with  them  substances  of  an  irritating  nature,  which  may 
give  to  the  particles  an  injurious  action  which  the  pure  carbon  granules 
themselves  would  not  possess.  Although  occasionally  the  coal  particles  were 
present  immediately  around  and  in  some  places  appeared  to  be  within  the 
capillary  vessels,  there  was  no  such  obstruction  of  the  blood  vessels  by  coal 
pigment  as  would  explain  the  death  of  liver  cells. 


THE  PATHOLOGICAL  EFFECTS  OF  ALCOHOL* 

Introduction. — In  considering  the  action  of  alcohol  upon  the  living  body, 
it  is  convenient  and  customary  to  distinguish  between  the  physiological,  the 
pharmacological,  and  the  pathological  action  or  effects  of  this  agent,  altliough 
in  a  broad  sense  all  marked  deviations  from  the  normal  condition  produced 
by  alcohol  are  pathological.  Inasmuch  as  previous  articles  in  this  book 
have  treated  of  the  composition  and  relative  toxicity  of  the  constituents  of 
alcoholic  beverages,  and  of  the  action  of  alcohol  on  the  digestion,  the  circu- 
lation, the  respiration,  and  the  nervous  and  muscular  activities,  this  article 
is  intended  to  be  a  concise  statement  of  the  pathological  effects  of  alcohol 
and  of  alcoholic  drinks  in  the  more  restricted  sense  of  the  term  "  patli- 
ological,"  and  especially  of  those  effects  which  are  characterized  by  demon- 
strable anatomical  changes  in  the  body. 

It  may  at  the  outset  be  stated  that  the  injurious  effects  of  alcohol  upon 
the  body  are  represented  only  in  part  by  known  anatomical  lesions,  for  we 
are  still  ignorant  of  the  anatomical  basis  of  many  of  the  morbid  manifesta- 
tions produced  by  this  substance.  With  improvements  in  methods  of  micro- 
scopical investigation  our  knowledge  in  this  respect  has  materially  increased, 
and  from  still  more  refined  methods  further  advance  in  the  same  direction 
may  be  expected. 

The  questions  of  primary  importance  concerning  the  effects  of  alcoholic 
beverages  relate  to  the  action  of  ethyl  alcohol,  which  is  the  chief  harmful 
constituent  of  such  drinks,  although  the  effects  of  other  possible  ingredients, 
such  as  the  flavoring  essences  and  the  higher  alcohols,  and  the  influence  of 
concentration  of  the  alcohol  are  by  no  means  to  be  ignored.  In  this  article, 
by  the  word  "  alcohol,"  unless  otherwise  specified,  ethyl  alcohol  is  to  be 
understood. 

Our  sources  of  information  concerning  the  morbid  effects  of  alcohol  are 
experim,ents  upon  animals  and  observations  upon  human  beings.  The  ex- 
perimental method  has  the  advantages  that  the  conditions  can  be  better 
controlled  and  are  less  complicated,  and  tlie  results,  therefore,  are  generally 
clearer  of  interpretation  than  in  the  case  of  observations  on  human  beings, 
but  great  caution  should  be  exercised  in  applying  directly  to  human  beings 
the  conclusions  derived  from  animal  experiments. 

'In:  Physiological  Aspects  of  the  Liquor  Problem,  Bost.  &  N.  Y.,  1903,  II, 
349-374. 

413 


414  PATHOLOGICAL  EFFECTS  OF  ALCOHOL 

I.  Results  of  Experimental  Investigations 

Alcohol  in  sufficient  quantities  is  a  poison  to  all  living  organisms,  both 
animal  and  vegetable.  Our  chief  interest  in  this  connection  is  with  those 
experimental  results  which  shed  light  upon  the  pathological-anatomical 
effects  of  alcoholic  drinks  upon  human  beings.  During  the  last  fifty  years 
many  experiments  to  elucidate  this  subject  have  been  made  upon  animals, 
most  frequently  upon  rabbits,  dogs,  and  swine.  Different  sorts  of  alcohol 
and  of  alcoholic  drinks  in  varying  doses  and  for  varying  lengths  of  time  have 
been  administered  to  animals  in  different  ways,  the  best  and  most  commonly 
employed  method  being  injection  into  the  stomach  through  a  soft  rubber 
tube  passed  down  the  gullet. 

An  elaborate  experimental  investigation,  extending  over  four  years,  of  the 
pathological  effects  of  alcohol  upon  rabbits  has  been  made  in  behalf  of  the 
Physiological  Sub-Committee  of  the  Committee  of  Fifty  by  Dr.  Julius 
Friedenwald  in  the  Pathological  Laboratory  of  the  Johns  Hopkins  Uni- 
versity and  Hospital.  Eeference  will  be  made  to  conclusions  derived  from 
these  experiments,  which  have  hitherto  been  published  only  in  part. 

The  symptoms  of  acute  alcoholic  intoxication  in  the  animals  named 
resemble  so  closely  those  in  human  beings  that  the  experimental  method 
would  seem  adapted  for  the  study  of  anatomical  changes  which  may  be 
produced  under  these  circumstances.  On  the  other  hand,  most  experi- 
menters record  unsatisfactory,  although  not  wholly  negative,  results  in  their 
attempts  to  reproduce  experimentally  the  characteristic  symptoms  and 
lesions  of  chronic  alcoholism  as  observed  in  human  beings. 

Experimental  Acute  Alcoholic  Intoxication. — Inasmuch  as  the  symptoms 
of  acute  alcoholic  intoxication  in  animals,  as  well  as  in  man,  are  referable 
almost  entirely  to  the  nervous  system,  it  is  not  surprising  to  learn  that  the 
only  significant  anatomical  changes  produced  by  this  condition  are  of  the 
nerve  cells  and  their  processes.  Hyperaemia  of  the  stomach  with  increased 
secretion  of  mucus  is  also  often  present,  especially  when  the  alcohol  is  given 
in  a  concentrated  form.  The  nervous  changes  are  of  such  a  nature  that  they 
can  be  detected  only  by  the  delicate  modem  methods  introduced  by  Golgi, 
Nissl,  and  Marchi  for  the  study  of  the  microscopical  characters  of  the 
nervous  system,  and  hence  our  knowledge  concerning  them  dates  back 
scarcely  a  decade.  Berkley's  paper  published  in  1895  and  preceded  only  by 
the  brief  articles  of  Vas  in  1894,  and  of  Dehio  in  1895,  which  were  based 
upon  examination  of  a  small  material,  is  the  first  systematic  and  elaborate 
study  by  modern  methods  of  the  changes  of  the  central  nervous  system  in 
cxperimentiil  acute  and  chronic  alcoholic  intoxication.  Dr.  Berkley's  ex- 
aminations were  made,  in  behalf  of  the  Committee  of  Fifty,  upon  the  brains 
and  spinal  cords  of  rabbits  used  in  Dr.  Friedenwald's  experiments.    Another 


PATHOLOGICAL  EFFECTS  OF  ALCOHOL  415 

valuable  investigation  of  the  influence  of  acute  alcoholic  poisoning  on  nerve 
cells  is  that  conducted  under  Dr.  Hodge's  direction  for  the  Committee  of 
Fifty  by  Colin  Stewart,  and  published  in  1896.  Among  later  investigators 
of  this  subject  may  be  mentioned  Marinesco  (1897),  Jaccotet  (1897),  Car- 
rara (1898),  H.  Braun  (1899),  and  Kleefeld  (1901). 

Two  different  kinds  of  lesion  of  the  nerve  cells  have  been  found  in  acute 
poisoning  of  animals  by  alcohol,  the  one,  revealed  by  the  Golgi  method,  being 
of  the  cellular  processes,  and  the  other,  shown  by  NissFs  stain,  being  of  the 
body  of  the  cells.  The  former,  described  as  "  the  moniliform  change,"  is 
characterized  by  the  appearance  of  irregular  swellings  or  varicosities  in  the 
course  of  the  protoplasmic  processes  of  some  of  the  nerve  cells,  associated 
with  partial  loss  of  the  delicate  bud-like  or  spinous  projections  normally 
present  on  these  processes.  The  other  change,  designated  "  chromatolysis," 
is  the  disintegration  of  the  small,  stainable  granules,  known  as  the  Nissl 
bodies,  which  can  be  demonstrated  by  certain  methods  of  hardening  and 
staining  within  normal  nerve  cells.  It  is  not  within  the  scope  of  this  article 
to  describe  the  finer  histological  details  of  these  lesions. 

The  extent  and  the  intensity  of  these  changes  in  the  nerve  cells  depend 
upon  the  depth  of  the  alcoholic  intoxication.  Nerve  cells  altered  in  the  ways 
described  have  been  found  in  the  cerebral  hemispheres,  the  cerebellum,  the 
medulla  oblongata,  the  spinal  cord,  and  the  sympathetic  ganglia,  but  even  in 
extreme  degrees  of  the  lesions  it  is  only  a  minority  of  the  cells  which  are 
affected.  Kleefeld  claims  that  the  moniliform  change  occurs  almost  instan- 
taneously, and  may  be  found  within  a  few  minutes  after  the  entrance  of 
toxic  doses  of  alcohol  into  the  circulation.  Stewart  found  beginning  chroma- 
tolysis in  nerve  cells  of  a  cat  killed  in  fifty  minutes  by  the  injection  of  a  large 
dose  of  alcohol  into  the  abdominal  cavity.  The  most  extensive  changes  have 
been  found  in  animals  subjected  to  repeated,  profound  intoxication. 

There  is  considerable  difference  of  opinion  concerning  the  interpretation 
of  these  changes  and  their  relation  to  the  symptoms  of  alcoholic  intoxication, 
but  the  weight  of  evidence  favors  the  view  that  they  cannot  be  satisfactorily 
utilized  to  explain  the  symptoms.  The  same  changes  occur  from  various 
causes  and  under  a  great  variety  of  conditions  which  have  nothing  in  com- 
mon with  the  phenomena  of  alcoholic  intoxication.  They  do  not  represent 
any  serious  or  permanent  damage  to  the  nerv-e  cells,  but  are  readily  recovered 
from  after  disappearance  of  the  causative  factor.  It  has  even  been  questioned 
whether  these  changes  are  really  of  a  degenerative  nature,  some  authors 
being  inclined  to  refer  them  to  abnormal  movements  of  protoplasm  or  other 
manifestations  of  cell  life. 

Experimental  Chronic  Alcoholism. — Since  the  publication  in  1851  of  the 
important  work  by  Magnus  Huss  on  chronic  alcoholism  many  experiments 


416  PATHOLOGICAL  EFFECTS  OF  ALCOHOL 

have  been  made  to  determine  the  effects  upon  animals  of  the  long-continued 
use  of  alcohol.  The  most  extensive  and  prolonged  series  of  experiments  of 
this  nature  hitherto  made  is  that  for  the  Committee  of  Fifty  by  Dr.  Frieden- 
wald  in  the  pathological  laboratory  of  the  Johns  Hopkins  University  and 
Hospital.  The  details  of  these  experiments  will  be  published  elsewhere. 
Most  of  the  one  hundred  and  twenty  rabbits  used  in  these  experiments  re- 
ceived daily,  through  a  soft  rubber  stomach  tube,  from  five  to  eight  cubic 
centimetres  of  alcohol  largely  diluted.  These  quantities  sufficed  to  induce 
within  half  an  hour  a  drunken  stupor  which  lasted  from  three  to  five  hours, 
tlie  animal  generally  appearing  well  on  the  following  day. 

Dr.  Friedenwald  observed,  as  other  experimenters  have  done,  marked  in- 
dividual variations  in  susceptibility  to  the  injurious  effects  of  the  continued 
use  of  alcohol.  While  the  tolerance  of  any  given  animal  could  not  be  posi- 
tively foretold,  young  rabbits,  pregnant  females,  and  those  weighing  under 
one  thousand  grammes  were  the  most  susceptible.  Certain  individuals 
were  found  to  be  so  resistant  that  they  seemed  capable  of  tolerating 'daily 
intoxicating  doses  of  alcohol  for  an  indefinite  period.  Thus,  one  rabbit 
was  given  alcohol  for  over  four  years,  receiving  in  this  time  over  four  litres 
of  absolute  alcohol  without  permanent  ill  effects ;  others  were  fed  with  alco- 
hol for  three  and  a  half  and  for  three  years.  These  animals  had  the  best  of 
care  and  were  kept  under  excellent  sanitary  conditions.  On  the  other  hand, 
some  of  the  rabbits  died  from  acute  intoxication  after  a  few  doses,  and  the 
majority  succumbed  after  shorter  or  longer  periods  of  time,  with  gradual 
loss  of  weight  and  exhaustion.  If  especial  care  was  taken  to  lessen  or  to 
intermit  the  dose  of  alcohol  when  the  animal  began  to  lose  weight,  it  was 
found  possible  later  to  increase  the  dose  and  to  keep  a  considerable  number 
of  the  rabbits  alive  for  an  indefinite  period.  Under  favorable  conditions 
the  animals  tended  to  gain  in  weight  when  taking  alcohol,  especially  during 
the  early  period. 

As  regards  the  pathological  effects,  there  have  been  considerable  differ- 
ences between  the  results  reported  by  various  experimenters.  Some  of  the 
earlier  experimenters  found  practically  no  anatomical  changes  in  animals 
to  which  intoxicating  doses  of  alcohol  had  been  fed  for  weeks  or  months. 
The  experiments  of  Dujardin-Beaumetz  and  Audige  (1879-1884)  on  swine, 
extending  over  three  years,  which  are  among  the  most  elaborate  and  pains- 
taking investigations  of  this  subject  ever  made,  yielded  practically  negative 
results,  so  far  as  pathological  lesions  are  concerned.  On  the  other  hand,  the 
more  recent  experimental  researches,  although  not  altogether  in  accord, 
have  in  general  been  more  fruitful  in  positive  results. 

While  these  discrepancies  are  at  present  partly  inexplicable,  some  at  least 
may  be  accounted  for  by  differences  in  the  animals  selected  for  cxperimenta- 


PATHOLOGICAL  EFFECTS  OF  ALCOHOL  417 

tion,  by  variations  in  the  quantity,  quality,  and  mode  of  administration  of 
the  alcohol,  by  the  duration  of  the  experiments,  by  the  technique  employed 
in  the  microscopical  examinations,  and  by  the  concentration  of  attention 
upon  changes  in  special  organs. 

It  is  to  be  noted  that  in  most  of  tlie  experiments  the  amount  of  alcohol 
given  at  a  single  dose  sufficed  to  produce  marked  symptoms  of  intoxication, 
this  quantity  being  in  ratio  to  the  body  weight  generally  much  greater  than 
that  taken  by  heavy  drinkers.  No  systematic  experiments  have  been  made 
to  determine  the  pathological  effects  upon  animals  of  the  long-continued 
use  of  alcohol  in  quantities  so  small  as  to  produce  no  manifest  symptoms  of 
intoxication ;  but  in  view  of  the  comparatively  meagre  results  in  the  experi- 
ments with  moderately  intoxicating  doses,  it  seems  improbable  that  experi- 
ments of  the  former  character  would  yield  positive  results. 

Naturally  the  attention  of  the  experimenters  has  been  drawTi  mainly  to 
the  examination  of  those  organs  which  are  known  to  be  most  frequently 
affected  in  man  in  cases  of  chronic  alcoholism,  namely,  the  stomach,  the 
liver,  the  kidneys,  the  heart  axid  blood-vessels,  and  the  nervous  system. 

Stomach. — Congestion  of  the  gastric  mucous  membrane  and  increased 
secretion  of  mucous  are  among  the  most  common  conditions  noted  by  the 
various  experimenters.  Haemorrhages,  erosions,  and  actual  ulceration  of  the 
stomach  have  also  been  repeatedly  recorded.  Several  experimenters  have 
reported  degenerative  changes  in  the  cells  of  the  gastric  tubules  and  chronic 
interstitial  inflammation  of  the  mucous  membrane. 

There  is  evidence  that  some  of  these  alterations,  especially  the  more  pro- 
found ones,  are  attributable  to  administration  of  the  alcohol  in  too  con- 
centrated a  form  and  sometimes  to  mechanical  injuries  inflicted  by  the 
stomach  tube. 

In  Friedenwald's  experiments  on  rabbits  there  was  frequently  observed 
during  life  a  gradual  reduction  in  the  amount  of  free  hydrochloric  acid  in 
the  gastric  contents.  In  some  cases  hyperaemia,  increased  secretion  of 
mucus,  and  fatty  degeneration  of  the  epithelial  cells  of  the  gastric  tubules 
were  found,  but  in  many  instances,  even  after  the  prolonged  use  of  diluted 
alcohol,  the  stomach  appeared  entirely  normal,  both  to  the  naked  eye  and 
under  the  microscope. 

As  a  rule,  no  patliological  changes  were  present  in  the  intestine. 

Liver. — Inasmuch  as  the  long-continued  excessive  use  of  alcoholic  drinks 
is  by  far  the  most  common  and  important  cause  of  cirrhosis  of  the  liver  in 
human  beings,  the  attention  of  experimenters  has  been  directed  especially 
to  the  condition  of  this  organ  in  chronic,  experimental  alcoholic  poisoning. 

Of  the  various  anatomical  changes  noted  by  the  different  experimenters, 
fatty  metamorphosis  of  the  liver  cells  is  the  one  most  frequently  recorded. 


418  PATHOLOGICAL  EFFECTS  OF  ALCOHOL 

This  change  is  not  usually  present  in  an  extreme  degree,  and  it  is  not  gen- 
erally associated  with  loss  of  the  cellular  nuclei  or  other  evidences  of  death 
of  cells.  It  readily  disappears  after  cessation  of  the  administration  of  alco- 
hol.   Hyperaemia  of  the  liver  is  not  uncommon. 

Actual  necrosis  or  death  of  the  liver  cells,  either  singly  or  in  groups, 
occasionally  occurs,  but  this,  at  least  in  marked  degree,  is  exceptional. 

An  increase  in  the  number  of  lymphoid  cells  in  the  interlobular  tissue  has 
been  found  by  a  minority  of  the  experimenters.  It  was  noticed  in  varying 
degree  in  some  of  Friedenwald's  experiments,  but  its  occurrence  was  incon- 
sistent and  rather  exceptional. 

Genuine  cirrhosis  of  the  liver  has  not  been  satisfactorily  reproduced  by 
the  experimental  use  of  alcohol.  It  was  present  in  one  of  the  rabbits  of 
Friedenwald's  early  experiments,  but  as  this  was  an  isolated  instance  of  its 
appearance,  it  is  not  certain  that  it  was  attributable  to  the  alcohol.  The  few 
experimenters  who  have  reported  successful  results  in  this  regard  have 
probably  mistaken  mere  accumulations  of  lymphoid  cells  for  early  stages  of 
cirrhosis,  or  have  not  excluded  changes  due  to  accidental  infections,  particu- 
larly from  unintended  injuries  of  the  stomach.  This  failure  to  produce 
experimetally  cirrhosis  of  the  liver  by  the  use  of  alcohol  cannot  be  at- 
tributed in  Friedenwald's  series  to  the  too  short  duration  of  the  experi- 
ments. It  lends  support  to  the  opinion  held  by  many  that  in  human  beings 
alcohol  acts  only  indirectly  in  leading  to  cirrhosis  of  the  liver,  or  that  special 
predisposing  or  associated  conditions  must  be  present  in  addition  to  the 
action  of  the  alcohol. 

Kidneys. — Most  of  the  experimenters  have  not  noted  serious  anatomical 
changes  in  the  kidneys,  but  von  Kahlden  in  a  careful  research  lays  especial 
emphasis  upon  lesions  of  this  organ  in  dogs.  He  describes  fatty  degener- 
ation and  necrosis  of  the  renal  epithelium,  hyperaemia  of  the  veins  and  capil- 
laries, haemorrhages,  and  transudation  of  an  albuminous  fluid,  and  con- 
siders that  with  longer  duration  of  the  experiments  a  chronic  interstitial 
nephritis  would  appear  as  a  result  of  these  grave  lesions. 

Seven  of  the  rabbits  in  Friedenwald's  series  of  experiments  had  marked 
albuminuria,  associated  in  five  cases  with  casts.  Fatty  degeneration  of  the 
epithelium  of  the  convoluted  and  Henle's  tubules  was  common,  although  not 
constant.  In  a  few  instances  there  was  necrosis  of  the  epithelium,  and 
atrophy  of  the  glomeruli.  On  the  other  hand,  a  number  of  the  rabbits 
showed  no  changes  in  the  kidneys  after  long-continued  use  of  alcohol.  An 
actual  chronic  interstitial  nephritis  was  not  produced. 

Heart,  Blood-Vessels,  and  Blood. — In  Friedenwald's  experiments  fatty 
degeneration  of  tlie  muscle  of  the  iicart  was  found  in  most  of  the  rabbits 
which  died  from  chronic  alcoholic  intoxication,  but  was  absent  in  those 
which  were  killed  after  cessation  of  the  use  of  lacoliol. 


PATHOLOGICAL  EFFECTS  OF  ALCOHOL  419 

In  these  experiments,  as  well  as  in  those  of  others,  now  and  then  a 
sclerotic  or  atheromatous  patch  was  found  on  the  inner  surface  of  the  aorta 
or  other  blood-vessel.  This  lesion  was  present,  however,  too  inconstantly  to 
be  attributed  with  any  certainty  to  the  action  of  the  alcohol,  especially  as 
similar  changes  occasionally  are  found  in  animals  which  have  not  received 
alcohol.  Petrov,  however,  describes  progressive  sclerosis  of  blood-vessels  in 
experimental  alcoholism. 

Fatty  degeneration  of  the  endothelial  cells  and  sometimes  of  the  smooth 
muscle  is  found  with  sufficient  frequency  in  the  blood-vessels  of  different 
organs  to  be  ascribed  to  the  effect  of  the  alcohol. 

Often  the  distribution  of  the  blood  does  not  differ  materially  from  the 
normal,  but  there  may  be  hyperaemia  of  certain  organs,  most  commonly  of 
the  stomach,  liver,  kidneys,  and  brain. 

Friedenwald  noted  in  many  instances  a  considerable  reduction  in  the  per- 
centage of  haemoglobin.  In  those  chronic  intoxications  which  terminated 
fatally  there  was  usually,  during  the  last  month  or  so  of  life,  a  distinct 
anaemia,  with  reduction  in  the  number  of  both  red  and  white  corpuscles. 
Fatty  degeneration  of  leucocytes  may  occur. 

Nervous  System. — The  more  recent  experimental  studies  of  the  patho- 
logical effects  of  alcohol  have  been  concerned  especially  with  the  condition  of 
the  central  and  the  peripheral  nervous  system.  In  animals,  dead  from 
chronic  alcoholic  poisoning,  changes  of  the  nerve  cells  have  been  found 
identical  with  those  described  under  "  Experimental  Acute  Alcoholic  Intoxi- 
cation "  (p.  414).  There  is  reason  to  think  that  these  changes  belong,  even 
in  the  chronic  cases,  to  the  more  immediate,  acute  effects  of  alcoholic  poison- 
ing, for  in  Friedenwald's  experiments  they  were  often  absent  in  animals 
which  did  not  die,  but  were  killed  in  the  course  of  the  experiments,  and  they 
were  not  observed  in  animals  allowed  to  live  a  few  days  after  the  alcohol  was 
stopped. 

Of  other  lesions  of  the  brain  and  spinal  cord  ascribed  to  chronic  alcohol- 
ism in  animals  Afanassijew  and  Braun  describe  fatty  and  vacuolar  degen- 
eration of  nerve  cells;  Braun  also  describes  a  vacuolar  rarefaction  of  the 
medullary  substance,  fatty  degeneration  of  the  myelin,  and  the  appearance 
of  fatty  granular  cells  along  the  blood-vessels,  and  Berkley  alterations  in  the 
calibre  and  walls  of  the  blood-vessels  and  the  peri-vascular  lymphatics,  and 
accumulations  of  leucocytes.  Small  haemorrhages  are  occasionally  found. 
None  of  these  changes  is  constant.  Some  of  the  rabbits  of  Friedenwald's 
experiments  which  were  killed  after  daily  intoxication  with  alcohol  for  over 
two  years  showed  practically  no  lesions  of  the  nervous  system. 

In  view  of  the  importance  of  peripheral  neuritis  in  the  pathology  of 
chronic  alcoholism  in  man,  much  interest  attaches  to  the  observations  of 


420  PATHOLOGICAL  EFFECTS  OF  ALCOHOL 

Spaink,  and  later  of  Braun,  who  found  both  in  rabbits  and  in  dogs  subjected 
to  chronic  poisoning  with  alcohol  degenerations  of  various  peripheral  nerves. 
Only  in  the  more  chronic  cases  was  this  degeneration,  which  is  characterized 
especially  by  breaking-up  of  the  myeline,  well  marked.  These  experimenters 
claim  to  have  observed  in  these  animals  most  of  the  nervous,  muscular,  and 
other  symptoms  characteristic  of  chronic  alcoholism  in  man.  Further  con- 
firmatory investigations  are  needed  before  these  results  can  be  unhesitatingly 
accepted,  especially  as  similar  extensive  changes  in  the  peripheral  nerves 
were  not  observed  in  Friedenwald's  experiments. 

Other  Organs. — Although  hyperaemia,  oedema  haemorrhages,  and  actual 
inflammation  of  the  lungs  have  been  described  as  results  of  alcoholism  in 
animals,  there  is  no  good  reason  for  this  interpretation.  Doubtless  in  many 
cases  these  lesions,  when  found,  were  attributable  to  the  accidental  escape  of 
alcohol  into  the  windpipe.  There  is  no  satisfactory  evidence  that  alcohol, 
administered  by  the  stomach,  acts  injuriously  upon  the  lungs  of  animals. 
In  Friedenwald's  rabbits  a  diffuse,  fine  deposition  of  fatty  granules  in  the 
epithelial  and  interstitial  cells  of  the  testicles  was  often  observed.  More 
profound  changes  in  these  organs,  even  atrophy,  induration,  and  softening, 
are  described  by  Bouin  and  Gamier  as  the  result  of  alcoholic  poisoning  of 
white  rats  for  eight  to  eleven  months ;  but  these  observations  need  confirma- 
tion before  acceptance.  The  same  caution  is  applicable  to  Sodokow's  state- 
ments concerning  changes  in  the  ovules  and  spermatozoa. 

Experimental  Investigations  of  the  Influence  of  Alcoholism  upon  Resist- 
ance to  Infection. — There  have  been  at  least  a  dozen  experimental  investiga- 
tions published  concerning  the  influence  of  alcohol  upon  susceptibility  to 
infection,  the  first  extensive  series  of  experiments  being  that  of  Dr.  Abbott, 
published  in  189G,  and  made  in  behalf  of  the  Committee  of  Fifty.  These 
various  experiments  are  in  remarkable  accord,  nearly  all  showing  that  ani- 
mals intoxicated  by  alcohol  are  more  susceptible  to  bacterial  infection  or  to 
toxines  than  are  normal  animals.  Eoos,  however,  found  no  increase  in  sus- 
ceptibility to  the  tubercle  bacillus  of  guinea  pigs  fed  with  wine,  and  Kogler, 
under  Gruber's  direction,  noted  a  favorable  influence  of  alcohol  upon  the 
survival  of  animals  treated  with  this  agent  during  the  stage  of  acute  collapse 
produced  by  intraperitoneal  injection  of  killed  cultures  of  Bacillus  prodigio- 
sus.  Delearde  has  found  that  the  process  of  experimental  immunization  is 
unfavorably  influenced  by  alcohol. 

Tiiese  researches  furnish  an  experimental  basis  for  the  generally  recog- 
nized lowering  of  resistance  to  many  infectious  diseases  manifested  by  alco- 
holic patients.  They  are  not  however,  decisive  as  to  the  usefulness  of  alcohol 
in  the  treatment  of  infectious  diseases  in  human  beings,  for  tlie  amount  of 
alcohol  used  in  experiments  proportionately  to  body  weight  far  surpasses 


PATHOLOGICAL  EFFECTS  OF  ALCOHOL  421 

that  generally  given  for  therapeutical  purposes,  and  the  question  is  one 
which  must  be  answered  by  clinical  experience. 

In  this  connection  may  be  mentioned  the  unfavorable  influence  of  alcohol 
upon  pregnant  females  observed  by  Friedenwald  in  his  experiments.  Of 
twenty  pregnant  rabbits  fed  with  alcohol  seventeen  aborted,  and  of  these 
eight  died  soon  afterward  of  septicaemia.  Nearly  all  of  the  young  which 
were  born  at  full  term  died  a  few  days  after  birth.  Laitinen  reports  a 
similar  experience  with  pregnant  guinea  pigs  intoxicated  with  alcohol. 

SUMMARY  OF  THE  PATHOLOGICAL  CHANGES  IN  EIXPERIMENTAL  ALCOHOLISM 

1.  There  are  no  satisfactory  experimental  data  to  determine  the  patho- 
logical effects  upon  animals  of  alcohol  or  of  alcoholic  beverages  taken  for  a 
long  time  in  quantities  which  produce  no  marked  symptoms  of  intoxication. 
In  most  of  the  experiments  the  amount  of  alcohol  administered  at  a  dose, 
in  proportion  to  body  weight,  considerably  exceeded  that  usually  taken 
even  by  heavy  drinkers. 

2.  Animals  exhibit  marked  individual  differences  in  their  susceptibility 
to  the  injurious  effects  of  the  prolonged  administraton  of  intoxicating  doses 
of  alcohol.  ^Yhile  certain  individuals  succumb  quickly,  others  may  be  kept 
alive  under  these  circumstances  for  at  least  four  years  without  presenting 
any  serious  anatomical  lesions  attributable  to  the  alcohol.  Between  the  ex- 
tremes there  are  all  gradations  in  susceptibility,  young  animals  and  pregnant 
ones  being  generally  the  most  susceptible. 

3.  In  acute  experimental  alcoholism  there  can  be  demonstrated  certain 
delicate  changes  in  the  nerve  cells,  which  readily  disappear  after  stopping 
the  alcohol. 

4.  The  experimental  reproduction  in  animals  of  certain  of  the  more 
characteristic  diseases  of  human  beings,  attributable  to  the  abuse  of  alcohol, 
such  as  cirrhosis  of  the  liver,  chronic  Bright's  disease,  and  arterio-sclerosis, 
has  not  been  satisfactorily  attained.  The  most  common  pathological  con- 
dition noted  in  experimental  chronic  alcoholism  of  animals  is  a  fatty  meta- 
morphosis affecting  especially  the  cells  of.  the  liver,  the  heart  muscle,  and 
the  kidneys.  This  lesion  soon  disappears  after  stopping  the  use  of  the 
alcohol.  Death  or  necrosis  of  limited  groups  of  cells  in  the  liver  and  kidneys 
may  occur,  but  is  inconstant,  and,  according  to  most  experimenters,  is  ex- 
ceptional. More  common  is  an  acute  or  chronic  catarrhal  gastritis,  but  this, 
is  often  absent  or  but  slight.  Changes  in  the  central  nervous  system,  similar 
to  those  in  acute  alcoholism,  as  well  as  certain  additional  ones,  may  be  pres- 
ent in  experimental  chronic  alcoholism.  There  may  also  be  degenerations 
of  the  peripheral  nerves.  Hyperaemia  and  small  haemorrhages  may  occur, 
especially  in  the  stomach,  the  kidneys,  and  the  brain.    In  view  of  considerable 


422  PATHOLOGICAL  EFFECTS  OF  ALCOHOL 

differences  in  the  results  reported  by  different  experimenters,  and  of  many 
still  unsolved  problems,  additional  experiments  upon  the  pathological  effects 
of  the  long-continued  use  of  alcohol  and  of  alcoholic  drinks  are  needed. 

5.  Alcoholic  intoxication  increases  the  susceptibility  of  animals  to  many 
infections,  and  influences  unfavorably  the  process  of  immunization.  Preg- 
nant rabbits  or  guinea  pigs  repeatedly  intoxicated  by  alcohol  are  likely  to 
abort,  and  to  die  soon  afterward  from  some  accidental  infection.  Many  of 
their  young  die  a  few  days  after  birth, 

II.  Alcohol  as  a  Cause  of  Human  Diseases 

It  is  universally  recognized  that  alcoholic  intemperance  is  the  direct  or 
the  contributory  cause  of  an  immense  amount  of  sickness  and  disability,  and 
of  a  very  large  number  of  deaths,  concerning  which,  for  obvious  reasons, 
mortality  returns  furnish  only  imperfect  and  partial  statistical  information. 

According  to  Vacher  the  Eegistrar-General's  Reports  for  England  and 
Wales  show  during  the  twenty  years  from  1881  to  1900  a  total  of  110,215 
deaths  due  to  chronic  alcoholism,  delirium  tremens,  and  cirrhosis  of  the 
liver,  these  being  the  only  causes  of  death,  registered  in  the  reports,  which 
directly  represent  the  mortality  from  alcoholic  intemperance.  These  deaths 
correspond  to  an  average  death-rate  per  million  living  for  the  twenty  years 
from  these  three  diseases  of  188.45,  that  among  the  male  population  between 
226.7,  and  that  among  the  female  population  152.6.  A  large  majority  of 
these  deaths  occurred  between  twenty-five  and  fifty-five  years  of  age,  when 
men  and  women  should  be  at  their  best.  During  the  twenty  years  there 
was  an  increase  in  the  mortality  from  each  of  these  diseases,  but  only  in 
the  case  of  chronic  alcoholism  was  this  very  remarkable.  The  three  causes 
of  death  included  in  these  statistics  by  no  means  represent  the  total  mor- 
tality from  alcoholic  intemperance,  for  the  agency  of  alcohol  in  the  causa- 
tion or  the  fatality  of  Bright's  disease,  diseases  of  the  heart  and  blood- 
vessels, apoplexy,  paralysis,  insanity,  pneumonia,  tuberculosis,  and  other 
diseases  is  not  recorded  in  these  or  in  most  other  mortality  returns. 

For  the  last  twelve  years  the  official  mortality  reports  from  the  larger 
Swiss  cities  contain  data  concerning  alcoholic  excess  as  a  contributory  as 
well  as  a  direct  cause  of  death.  The  statistics  (cited  from  Delbriick)  from 
the  fifteen  largest  Swiss  cities  for  the  eight  years  from  1891  to  1898  show 
that  in  6.4  per  cent  of  all  deaths  of  persons  over  twenty  years  of  age 
alcoholism  was  either  the  direct  cause  or  a  contributory  cause.  The  per- 
centage is  10  for  men  over  twenty  years  old.  Different  places  and  countries, 
of  course,  show  marked  differences  in  the  mortality  from  intemperance. 
Switzerland  ranks  among  countries  with  a  medium  consumption  of  alcohol. 

Individual  predisposition  and  also  predisposition  of  special  organs  of  the 


PATHOLOGICAL  EFFECTS  OF  ALCOHOL  423 

body  are  important  factors  in  the  etiology  and  pathology  of  alcoholism.  It 
is  a  matter  of  common  experience  that  many  persons  drink  beer,  wine,  and 
spirits  in  moderation  throughout  a  long  life  without  apparent  impairment 
of  the  general  health.  There  are,  however,  others  so  extremely  susceptible 
to  the  action  of  alcohol  that  they  are  intoxicated  by  quantities  so  small  as  to 
be  without  manifest  effect  upon  most  persons.  In  some  individuals,  also, 
the  symptoms  of  intoxication  assume  an  unusual  so-called  pathological  type. 
Unusual  susceptibility  to  the  toxic  influence  of  alcohol,  as  well  as  a  morbid 
craving  for  alcoholic  liquors  in  increasing  quantities,  have  been  attributed 
in  many  instances  to  an  inherited  or  acquired  degeneracy  or  instability  of 
the  nervous  system,  but  the  opinions  of  authorities  are  much  divided  as  to 
the  relative  importance  to  be  attached  to  this  factor  in  the  causation  of 
alcoholism.  The  periodical  excessive  drinking  which  characterizes  dipso- 
mania is  now  generally  regarded  as  a  manifestation  of  a  disease  which  some 
physicians  consider  to  be  analogous  to  epilepsy.  Of  the  injurious  effects  of 
the  continued  use  of  even  small  quantities  of  alcoholic  liquors  upon  infants 
and  children  Demme  and  others  have  brought  abundant  evidence. 

The  importance  of  predisposition  is  further  illustrated  by  the  familiar 
fact  that  some  persons  after  a  relatively  short  period  of  immoderate  indul- 
gence in  alcoholic  liquors  present  the  symptoms  and  lesions  of  chronic 
alcoholism,  whereas  others  under  the  same  conditions,  or  perhaps  even  more 
intemperate,  are  affected  only  after  a  much  longer  interval  or,  it  may  be,  not 
at  all.  Evidence  of  predisposition  on  the  part  of  organs  is  furnished  by  the 
remarkable  differences  in  the  manifestations  and  the  localization  of  alcoholic 
diseases  in  different  persons,  so  that  in  one  the  kidney,  in  another  the  liver, 
in  another  the  heart,  and  in  still  another  the  brain  is  the  organ  chiefly 
damaged  by  alcohol.  These  differences  can  be  explained  only  in  part  by  the 
kind  and  concentration  of  the  alcoholic  beverages  used. 

There  being  no  constant  and  definite  relation  between  the  amount  of 
alcohol  consumed  and  its  pathological  effects,  it  is  difficult  to  make  state- 
ments which  shall  be  both  precise  and  truthful  concerning  possible  patho- 
logical effects  of  what  is  ordinarily  called  "moderate  drinking."  This  sub- 
ject is  one  concerning  which  widely  divergent  views  have  been  expressed 
even  by  those  whose  opinions  are  authoritative  in  medicine.  Its  scientific 
investigation  encounters  peculiar  difficultes,  and  at  present  the  established 
facts  are  too  few  to  permit  secure,  broad  generalizations.  The  increasing 
recognition,  especially  within  recent  years,  of  the  importance  of  this  matter, 
is  sure  to  lead  to  more  exact  knowledge  concerning  it,  but  it  will  probably 
be  a  considerable  time  before  an  entire  agreement  of  medical  opinion  in  this 
regard  is  reached. 

A  difficulty  at  the  beginning  is  encountered  in  attempting  to  define  moder- 
ation in  drinking.    What  is  moderate  for  one  person  may  be  immoderate  for 


424  PATHOLOGICAL  EFFECTS  OF  ALCOHOL 

another.  The  discussion  of  this  -fundamental  aspect  of  the  suhject  belongs 
to  the  consideration  of  the  physiological  and  the  pharmacological  action  of 
alcohol,  and  has  been  presented  in  other  articles,  particularly  in  Dr.  Abel's 
"  Review  of  the  Pharmacological  Action  of  Ethyl  Alcohol,"  which  were 
published  in  the  book  on  "  Physiological  Aspects  of  the  Liquor  Problem." 
There  it  has  been  pointed  out  that  the  closer  analysis  of  the  physiological 
effects  of  alcohol,  especially  upon  the  nervous  centres,  has  led  many  to  adopt, 
in  comparison  with  earlier  standards,  a  considerable  reduction  in  the  quan- 
tity of  alcohol  which  may  be  properly  designated  as  "  moderate,"  that  is,  the 
quantity  which  may  be  habitually  taken  without  bad  results  of  any  kind.  It 
may  here  be  said  that  increased  knowledge  of  the  pathological  effects  upon 
the  body  of  the  continued  use  of  alcoholic  beverages  has  drawn  many  physi- 
cians who  have  carefully  studied  the  subject  to  a  similar  conclusion,  the 
demonstration  of  the  causative  relation  of  beer-drinking  to  diseases  of  the 
heart  and  arteries  having  been  of  especial  influence  upon  medical  opinion  in 
this  regard.  Alcoholic  diseases  are  certainly  not  limited  to  persons  recog- 
nized as  drunkards.  Instances  have  been  reported  in  increasing  number  in 
recent  years  of  the  occurrence  of  diseases  of  the  circulatory,  renal,  and  ner- 
vous systems,  reasonably  or  positively  attributed  to  the  use  of  alcoholic 
liquors,  in  persons  who  never  became  really  intoxicated  and  were  regarded 
by  themselves  and  by  others  as  "  moderate  drinkers."  Striimpell  believes 
that  the  daily  consumption  of  three  to  four  litres  of  beer  will  eventually  act 
injuriously  upon  the  heart.  No  precise  figures  are  available  concerning  the 
frequency  with  which  alcoholic  indulgence  in  its  lesser  degrees  causes  disease. 
It  is  well  established  that  the  general  mortality  from  diseases  of  the  liver, 
kidney,  heart,  blood-vessels,  and  nervous  system  is  much  higher  in  those 
following  occupations  which  expose  them  to  the  temptation  of  drinking 
than  in  others. 

The  bodily  injur}'  inflicted  by  alcoholic  abuse  may  be  entirely  latent  until 
it  is  made  manifest  by  some  accessory  circumstance.  Thus  delirium  tremens, 
neuritis,  and  other  nervous  manifestations  of  alcoholism  often  make  their 
first  appearance  as  an  accompaniment  or  sequel  of  some  acute  febrile  disease, 
such  as  pneumonia,  or  of  traumatism,  loss  of  blood,  emotional  shocks,  or 
other  affection.  Or  the  bad  effects  of  immoderate  drinking  may  be  unsus- 
pected until  they  influence  unfavorably  the  course  and  outcome  of  some  in- 
fectious disease  or  of  a  surgical  operation. 

Alcohohsm,  as  pointed  out  by  Striimpell,  represents  the  summation  of 
injuries  inflicted  upon  the  tissues  of  the  body  by  alcohol,  each  injury  being 
perhaps  minimal  in  amount  but  the  total  constituting  serious  disease.  It  is 
not  necessary  to  consider  here  the  various  theories  concerning  the  mode  of 
action  of  alcohol  as  a  poison,  or  the  extent  to  which  it  does  injury  by  acting 


PATHOLOGICAL  EFFECTS  OF  ALCOHOL  425 

directly  as  such  upon  the  cells,  or  indirectly  through  nutritive  or  other  dis- 
turbances. In  one  way  or  another  most  of  the  organs  and  tissues  of  the  body 
may  become  the  seat  of  morbid  changes  attributable  to  the  poisonous  action 
of  alcohol.  For  the  purposes  of  this  article  it  is  not  necessary  to  at+empt 
more  than  a  brief  specification  of  the  more  characteristic  and  common  path- 
ological effects  of  alcohol.  None  of  the  lesions  of  either  acute  or  chronic 
alcoholism  is  absolutely  pathognomonic  of  this  condition,  but  in  many  cases 
of  death  from  chronic  alcoliolism  the  anatomical  changes  in  their  entirety 
are  sufficiently  characteristic  to  establish  a  probable  diagnosis  without 
knowledge  of  the  history  of  the  case. 

The  poisonous  effects  of  alcohol  may  be  referred  to  the  following  classes 
of  morbid  change,  which  may  occur  either  singly  or  in  combination:  (1) 
disturbances  of  function,  (2)  irritative  effects  marked  by  hyperaemia,  with 
which  may  be  associated  haemorrhages  and  transudation  of  serum,  (3) 
cellular  degenerations  of  various  kinds,  (4)  production  of  new  connective 
tissue,  (5)  abnormal  metabolism,  characterized  especially  by  increased  for- 
mation of  fat  or  deposit  of  fat  in  abnormal  situations.  When  brought 
directly  in  a  concentrated  form  into  contact  with  the  tissues  alcohol  is  an 
inflammatory  irritant.  The  most  important  and  characteristic  pathological 
action  of  alcohol  is  that  of  a  cellular  poison.  It  is  probable  that  the  new 
growth  of  fibrous  tissue  in  certain  alcoholic  diseases,  especially  in  cirrhosis 
of  the  liver,  is  consecutive  to  a  primary  degeneration  or  death  of  cells, 
although  this  opinion  is  disputed. 

In  the  rare  instances  of  fatal  acute  alcoholic  poisoning,  when  a  large 
quantity  of  strong  spirit  is  taken  at  once,  no  characteristic  lesions  are  found 
after  death.  There  may  be  redness  and  inflammation  of  the  stomach  and 
congestion  and  haemorrhages  in  the  brain,  the  lungs,  and  perhaps  other 
organs,  but  these  changes  are  not  invariably  present,  and  they  are  in  no  way 
diagnostic.  We  have  experimental  evidence,  which  has  already  been  pre- 
sented, that  acute  alcoholic  intoxication  causes  certain  changes  of  a  transi- 
tory nature  in  the  nerve  cells,  and  similar  changes  have  been  found  in 
human  beings  in  the  acute  cerebral  disorders  of  alcoholism. 

CHRONIC    ALCOHOLISM 

Alimentary  and  Bespiratory  Tracts. — Chronic  catarrhal  inflammation  of 
the  stomach  is  a  common  affection  of  alcoholic  patients,  but  the  lurid  descrip- 
tions and  pictures  of  the  drunkard's  stomach  in  certain  popular  or  pseudo- 
scientific  "  temperance  "  tracts  and  books  are  drawn  from  the  imagination 
and  not  from  nature.  There  may  also  be  intestinal  catarrh,  but  usually  no 
marked  lesions  are  found  in  the  intestine,  except  in  cases  of  cirrhosis  of  the 
liver.  Catarrh  of  the  pharynx,  larynx,  and  bronchi  is  common  in  alcoholic 
patients. 
30 


426  PATHOLOGICAL  EFFECTS  OF  ALCOHOL 

Liver. — Cirrhosis  of  the  liver,  although  not  the  most  common,  is  the 
most  characteristic  pathological-anatomical  condition  produced  by  alcohol. 
The  liver  is  hard  and  nodular,  and  usually  reduced  in  size,  although  it  may 
be  larger  than  normal.  The  microscope  shows  a  new  growth  of  connective 
tissue  between  the  liver  lobules  and  atrophy  of  liver  cells,  which  may  also  be 
fatty.  The  immoderate  use  of  alcohol  is  the  cause  of  probably  over  ninety 
per  cent  of  the  cases  of  hepatic  cirrhosis,  and  some  think  that  it  is  the  sole 
cause.  This  disease  is  the  result  especially  of  drinking  strong  spirits,  being 
rare  in  beer  drinkers,  although  not  so  infrequent  in  France  from  excessive 
use  of  wines.  The  disease  is  sometimes  called  'Hhe  gin-drinker's  liver." 
Cirrhosis  of  the  liver  was  found  by  Formad  in  only  six  of  250  postmortem 
examinations  on  confirmed  drunkards  who  had  died  suddenly  from  the  effects 
of  alcohol.  Although  other  statistics  show  a  much  higher  percentage  of 
cases,  this  disease  is  upon  the  whole  a  relatively  infrequent  form  of  chronic 
alcoholism,  except  in  regions  where  excessive  drinking  of  strong  spirits 
prevails.  Deposition  of  fat  in  the  liver  cells  is  common  in  alcoholism,  and 
large  fatty  livers,  as  well  as  cirrhotic  livers,  are  found  in  drunkards. 

Pancreas. — With  or  without  cirrhosis  of  the  liver,  chronic  interstitial  in- 
flammation of  the  pancreas  may  be  the  result  of  alcoholic  intemperance.  In 
eight  of  tliirty  cases  of  this  disease  studied  by  Opie  there  was  a  historv'  of 
alcoholic  excess,  but  in  three  of  these  cases  the  affection  was  only  indirectly, 
if  at  all,  referable  to  the  use  of  alcohol. 

Kidneys. — There  has  been  much  discussion  concerning  the  effect  of 
alcohol  upon  the  kidneys.  Large  hyperaemic  kidneys  are  found  with  great 
frequency  in  those  who  drink  beer  to  excess,  but  this  is  a  condition  of  func- 
tional hypertrophy  rather  than  of  actual  disease,  the  kidneys  being  called 
upon  for  extra  work  in  eliminating  the  excessive  amount  of  fluid  taken  into 
the  circulation.  The  evidence,  however,  is  strong  that  alcoholic  excess  is 
injurious  to  the  kidneys.  The  observations  of  Glaser  made  in  1891  have 
since  been  repeatedly  confirmed,  that  the  urine,  even  after  a  single  alcoholic 
excess,  often  contains  abnormal  elements,  such  as  leucocytes,  casts,  and 
crystals  of  oxalate  of  lime  and  of  uric  acid,  indicative  of  transient  irritation 
or  even  slight  inflammation  of  the  kidneys.  The  experimental  evidence 
upon  this  subject  furnished  by  von  Kahlden  and  by  Friedenwald  has  already 
been  cited  (p.  418).  Although  some  English  authors,  following  Anstie  and 
Dickinson,  deny  any  causative  relation  of  alcoholic  abuse  to  Bright's  disease, 
Striimpell  regards  renal  disorders  as  the  most  common  of  all  tlie  pathological 
effects  of  alcohol.  The  weiglit  of  authority  and  of  evidence  supports  the 
view  that  excessive  indulgence  in  alcoholic  liquors,  fermented  as  well  as  dis- 
tilled, is  an  important  cause  of  chronic  Bright's  disease,  especially  of  the 
small,  granular  kidney.    Striimpell  describes  also  a  form  of  acute  nephritis 


PATHOLOGICAL  EFFECTS  OF  ALCOHOL  437 

which  may  rarely  result  from  the  long-continued  use  of  alcohol,  and  occa- 
sionally passes  into  the  chronic  forai. 

Heart. — Disorders  of  the  heart  are  among  the  most  important  manifesta- 
tions of  chronic  alcoholism,  these  depending  not  so  much  upon  any  direct 
injury  inflicted  upon  the  heart  by  alcohol  as  upon  associated  conditions 
resulting  from  alcoholic  abuse.  Bollinger  and  Bauer  in  Munich  were  the 
first  prominently  to  call  attention  to  the  frequency  of  hypertrophied  and 
dilated  hearts  in  those  who  drink  large  quantities  of  beer.  This  so-called 
"  Munich  beer-heart,"  which  is  commonly  associated  with  the  "  beer-kidney," 
is  probably  the  result  mainly  of  the  extra  demand  upon  the  heart  for  work  in 
propelling  the  excessive  volume  of  fluid  in  the  vessels.  The  compensation 
thus  established  is  likely  sooner  or  later  to  be- broken,  and  then  appear  serious 
symptoms  referable  to  cardiac  insufficiency.  Other  causes  of  hypertrophy 
of  the  heart  in  alcoholic  patients  are  sclerosis  of  the  arteries  and  chronic 
Bright's  disease.  Chronic  myocarditis,  or  new  growth  of  fibrous  tissue  in 
the  muscle  of  the  heart,  although  sometimes  ascribed  to  the  direct  action  of 
alcohol  on  the  heart,  is  rather  the  result  of  disease  of  the  arteries  of  the 
heart. 

Fatty  degeneration  of  the  heart  muscle  may  be  caused  by  alcoholic  excess, 
but  a  more  important  condition  clinically  is  the  overgrowth  of  adipose  tissue 
upon  the  surface  and  in  the  substance  of  the  heart,  which  is  found  particu- 
larly in  association  with  the  general  obesity  of  some  cases  of  chronic  alcohol- 
ism. This  latter  condition  may  interfere  seriously  with  the  normal  action 
of  the  heart. 

Blood-Vessels. — Alcohol  is  usually  regarded,  and  probably  correctly,  as 
one  of  the  causes  of  sclerosis  or  atheromatous  degeneration  of  the  arteries,  a 
disease  of  great  clinical  importance  and  attended  by  varied  symptoms  and 
organic  lesions  according  to  the  particular  arteries  chiefiy  affected.  In  this 
way  alcoholic  excess  may  stand  in  a  causative  relation  to  cerebral  disorders, 
such  as  apoplexy  and  paralysis,  and  also  to  diseases  of  the  heart  and  of  the 
kidneys.  Dilatation  of  the  veins,  particularly  about  the  nose  and  face,  are, 
together  with  acne  rosacea,  familiar  manifestations  of  chronic  alcoholism, 
although  they  may  occur  quite  independently  of  this  condition. 

Nervous  System. — The  special  toxic  action  of  alcohol  is,  in  the  first  in- 
stance, upon  the  higher  nervous  centres,  a  fact  which  is  manifest  enough  in 
the  familiar  symptoms  of  a  drunken  fit.  Although  the  special  affinity  of 
alcohol  for  the  nervous  system  has  long  been  known,  the  most  interesting 
and  important  clinical  and  pathological  studies  of  alcoholism  in  recent  years 
have  related  to  this  subject,  and  have  added  materially  to  our  knowledge. 
These  researches  have  shown  that  the  relationship  of  alcohol  to  mental  dis- 
orders and  other  disturbances  of  the  nervous  system  is  in  many  instances  less 


428  PATHOLOGICAL  EFFECTS  OF  ALCOHOL 

simple  and  direct  than  was  formerly  and  is  still  often  represented.  A 
problem  of  fundamental  importance,  as  yet  awaiting  final  solution,  is  the 
determination  of  the  part  to  be  assigned  to  underlying  inherited  or  acquired 
constitutional  defects  of  the  body,  chiefly  of  the  nervous  system,  in  the 
causation  and  the  pathology  of  the  various  disorders  of  the  nervous  system 
caused  by  or  associated  with  alcoholic  excess.  That  this  part  is  a  very 
important  one  cannot  be  questioned,  but  the  limits  to  be  assigned  to  it  are  at 
present  uncertain.  Both  the  general  and  the  statistical  statements  current 
in  many  medical  as  well  as  popular  writings  upon  the  causative  relation  of 
alcohol  to  insanity,  to  epilepsy,  and  to  certain  other  nen'ous  diseases  are 
often  of  little  value  with  reference  to  the  question  of  causation  of  these 
diseases  in  previously  normal  persons  by  alcoholic  poisoning. 

It  is  important  to  know  that  the  immoderate  drinking  of  alcoholic  liquor 
may  be  the  first  symptom  of  some  disease  which,  when  later  recognized,  is 
erroneously  ascribed  to  alcohol  as  the  cause.  It  is  furthermore  established 
that  many  of  the  mental  and  nervous  disorders  of  alcoholism,  while  they  are 
attributable  to  the  toxic  action  of  alcohol,  are  dependent  in  large  measure 
upon  an  underlying  psychopathic  constitution,  excessive  indulgence  in 
alcohol  rarely  producing  certain  of  these  disorders  in  persons  of  normal 
constitution.  Inebriety  in  the  parents  or  more  remote  ancestors  ranks 
among  the  important  causes  of  this  inherited  instability  of  the  nervous 
centres.  After  making  the  necessarily  large,  but  not  precisely  definable 
allowance  for  the  share  of  inherited  or  acquired  organic  or  constitutional 
defects  in  the  etiology  of  the  nervous  manifestations  of  alcoholism,  there 
still  remain  cases  enough  in  which  alcoholic  poisoning  is  the  cause  of  serious 
disease  of  the  brain,  spinal  cord,  and  nerves  in  persons  of  previously  normal 
constitution,  so  far  as  can  be  ascertained. 

Much  has  been  done  in  recent  years  by  psychiatrists  in  the  careful  analysis 
of  the  precise  psychical  defects  characteristic  of  the  various  alcoholic  psy- 
choses, and  in  this  way  the  features  particularly  distinctive  of  the  mental 
disturbances  due  to  alcoholic  poisoning  have  been  more  sharply  defined  than 
was  formerly  the  case.  Investigations  of  this  nature  have  been  made  by 
Wernicke,  Kraepelin,  Bonhoeffer,  Cramer,  and  others  on  delirium  tremens, 
alcoholic  neuritis,  with  the  corresponding  cerebral  and  spinal  diseases, 
especially  chronic  alcoholic  delirium  or  Korsakow's  psychosis,  acute  hallu- 
cinatory mania,  the  "  pathological  "  drunken  paroxysm  of  chronic  alcoholics, 
attended  often  with  acts  of  violence,  and  alcoholic  epilspsy,  but  it  is  not 
within  the  scope  of  this  article  to  attempt  a  consideration  of  these  interesting 
results. 

Correspondingly  sharp  anatomical  definitions  of  the  various  alcoholic 
diseases  of  the  nervous  system  are  still  lacking.    The  pathological  lesions  of 


PATHOLOGICAL  EFFECTS  OF  ALCOHOL  429 

the  brain  found  with  greater  or  less  frequency  in  cases  of  chronic  alcoholism 
are  thickening,  opacity,  and  adhesions  of  the  membranes,  chronic  haemor- 
rhagic  pachymeningitis,  transudation  of  serum,  atrophy  of  the  cerebral  con- 
volutions, a  granular  condition  of  the  ependyma,  atheromatous  arteries,  and 
increase  of  neuroglia  in  the  superficial  layers  of  the  cortex.  These  lesions 
belong  to  chronic  alcoholism  as  such  rather  than  to  any  one  of  tlie  special 
alcoholic  diseases  of  the  brain.  In  the  acute  alcoholic  psychoses,  of  which 
delirium  tremens  is  the  most  common  and  familiar  type,  the  modem  histo- 
logical technique,  particularly  the  Nissl  and  the  March!  methods,  have  re- 
vealed changes  in  the  nerves  and  the  nerve  cells  of  the  brain  and  spinal  cord, 
but  the  functional  significance  of  these  alterations  is  not  at  present  well 
understood. 

Since  the  investigations  of  Leyden  and  of  Moeli  about  twenty  years  ago, 
alcoholic  neuritis  has  been  recognized  as  an  important,  although  not  very 
common,  manifestation  of  chronic  alcoholism.  The  paralyses,  disturbances 
of  sensation,  ataxia,  and  other  symptoms  of  the  disease  had  been  previously 
noted.  Recent  studies,  particularly  those  of  Oppenheim,  Gudden,  and  Cole, 
have  led  to  the  important  conclusion  that  peripheral  neuritis  is  only  one 
part  of  an  affection  which  may  implicate  the  nerve  cells  and  their  processes 
throughout  the  whole  nervous  system.  In  some  cases  the  peripheral  neurones, 
in  others  the  central  neurones  are  chiefly  affected,  but  the  degeneration  may 
affect  in  a  single  case  various  groups  of  neurones  in  the  brain  and  in  the 
spinal  cord  and  ganglia,  including  widely  distributed  peripheral  nerves. 
The  lesion  in  all  cases  is  primarily  a  degenerative  one.  The  results  of  tliese 
researches  bring  into  close  relationship  various  alcoholic  diseases  of  the  brain, 
the  spinal  cord,  and  the  peripheral  nerves,  especially  delirium  tremens,  Kor- 
sakow's  psychosis,  and  multiple  neuritis.  The  underlying  condition  is  a 
toxaemia  induced  by  alcoholic  excess.  It  is  especially  in  this  group  of 
affections  that  the  cooperation  of  various  contributory  or  exciting  causes, 
such  as  pneumonia,  tuberculosis,  or  other  infection,  shock,  surgical  injury, 
privation,  etc.,  is  most  apparent.  The  patient  may  have  been  addicted  to 
alcoholic  excess  for  years,  but  the  introduction  of  one  of  these  accessory 
causes  suddenly  gives  rise  to  the  outbreak  of  one  of  these  disorders  of  the 
nervous  system. 

In  this  connection  may  be  mentioned  various  disturbances  of  vision  which 
are  often  associated  with  chronic  alcoholism  and  which  are  referred  by 
Uhthoff  mainly  to  changes  in  the  optic  nerves  or  their  terminations. 

The  excessive  use  of  absinthe  and  other  cordials  and  liqueurs  is  particu- 
larly injurious  to  the  nervous  centres,  for  here  the  flavoring  essences  in  vary- 
ing degree,  as  well  as  the  alcohol,  are  poisonous  to  the  nerve-cells.  Epileptic 
disorders  may  be  caused  ])y  the  immoderate  use  of  this  class  of  alcoholic 
liquors. 


430  PATHOLOGICAL  EFFECTS  OF  ALCOHOL 

Disorders  of  Metabolism,. — One  of  the  symptoms  of  chronic  alcoholism, 
most  common  in  beer-drinkers,  is  obesity.  Adipose  tissue  may  appear  in 
situations  where  it  is  not  normally  present,  the  most  dangerous  localization 
in  this  regard  being  between  the  muscle  fibres  of  the  heart.  Much  of  the 
fine,  molecular  fat  deposited  in  the  hepatic  and  other  cells  is  the  result  of 
abnormal  metabolism  of  the  fats  rather  than  of  a  true  fatty  degeneration. 
An  excess  of  fatty  particles  in  the  blood  of  drunkards  has  been  observed. 

The  use  of  alcoholic  liquor,  especially  in  the  form  of  the  stronger  wines, 
and  heavy  beer  or  porter  is  a  well-recognized  cause  of  gouty  manifestations 
in  those  predisposed  by  inheritance  to  this  disease. 

Striimpell  was  the  first  to  call  attention  to  the  influence  of  beer  in  inter- 
fering with  the  oxidation  of  sugar  in  the  body.  He  observed  in  certain  cases 
that  the  drinking  at  once  of  as  much  as  1^  to  2  litres  of  beer  was  followed 
by  a  transitory  alimentary  glycosuria.  These  observations  have  since  been 
confirmed  and  extended.  Striimpell  recognized  a  special  form  of  diabetes 
mellitus  due  to  alcohol,  and  he  brings  the  three  conditions — obesity,  gout, 
and  diabetes — into  a  group  of  correlated  alcoholic  disorders  of  metabolism. 

Lowered  Resistance  to  Disease. — A  much  larger  number  of  the  victims  of 
alcoholic  intemperance  die  of  some  infectious  disease  than  of  the  special 
alcoholic  affections.  Attention  has  repeatedly  been  called  in  this  article  to 
the  lowering  of  the  resistance  of  alcoholic  patients  to  many  infectious  dis- 
eases, and  the  experimental  data  bearing  upon  this  point  have  been  sum- 
marized. This  lowered  resistance  is  manifested  both  by  increased  liability 
to  contract  the  disease  and  by  the  greater  severity  of  the  disease.  Physicians 
generally  recognize  the  graver  prognosis  of  pneumonia,  cholera,  erysipelas, 
and  other  infections  in  persons  who  habitually  drink  to  excess  than  in  others. 

The  belief  was  once  widely  held  that  those  who  indulge  freely  in  alcoholic 
liquors  thereby  acquire  a  certain  degree  of  protection  from  tuberculosis,  but 
this  opinion  is  now  completely  discredited.  Alcoholism,  if  it  does  not 
actually  predispose  to  tuberculosis,  as  some  believe,  certainly  furnishes  no 
protection  against  it.  The  course  of  tuberculous  disease  in  alcoholic  patients 
is  often  more  rapid  than  usual. 

REFERENCES 

Abbott:    The  Journal  of  Experimental  Medicine,  1896,  I,  447. 

Afanasijew:    Ziegler's  Beitrage,  1890,  VIII,  p.  443. 

Anstie:    Alcoholism,  System  of  Medicine  (Reynolds).    London,  1868,  II,  p.  63. 

Baer,  A.:     Der  Alcoholismus.     Berlin,  1878. 

Bauer  and  Bollinger:   Ueber  idiopathische  Hehzvergrosserung.    Miinchen,  1893. 

Berkley:    Brain,  1895,  XVIII,  p.  473. 

Bonhoeffer:    Die  akuten  Geisteskrankheiten  der  Gewohnheitstrinker.    Jena,  1901. 

Bouin  and  Gamier.   Compt.  rend.  Soc.  de  biol.    Paris,  1900,  LII,  p.  23. 


PATHOLOGICAL  EFFECTS  OF  ALCOHOL  431 

Braun,  H. :    Ueber  die  experimentell  durch  chronische  Alkoholintoxikation  her- 

vorgerufenen  Veranderlungen  im  zentralen  und  periplieren  Nervensystem. 

Tubingen,  1899. 
Carrara:    Abstract  in  Jahresb.  iib.  d.  Leistungen  und  Fortschritte  a.  d.  Gebiete 

der  Neurologie  u.  Psychiatrie,  1898,  II,  p.  222. 
Cramer:  Monatsschr.  f.  Psychiatrie  u.  Neurologie,  1903,  XIII,  p.  36. 
Cole:    Brain,  1902,  Part  XCIX,  p.  326. 

Dehio:    Centralbl.  f.  Nervenheilk.  u.  Psychiatrie,  1895,  VI,  p.  113. 
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Kleefeld:    Journ.  de  physiol.  et  path,  gen.,  1901,  No.  4,  p.  563. 
Kogler:    See  Gruber. 
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Korsakow:    Abstr.  in  Arch,  di  psichiat.     Torino,  1890,  XI,  p.  279. 
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Sodokow  [Russian].    These  de  St.  Petersb.  Acad.  Imp.  Med.  Milit.,  Feb.,  1902. 
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sondere  das  peripherische  Nervensystem.     Inaug.-Diss.     Jena,  Published  in 

Amsterdam,   1890. 
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in  d.  11.  allgem.  Sitzung  d.  65.  Versamml.  deutscher  Naturforscher  u.  Aerzte 

zu  Nurnburg  am  13  Sept.,  1893.    2  Aufl.  Leipzig,  1898. 
UhthofE:     v.  Grafe's  Archiv,  XXXII,  pp.  95;    257. 
Vacher:    The  Practitioner,  1902,  LXIX,  p.  594. 
Vas:    Arch.  f.  exp.  Path.  u.  Pharm.,  1894,  XXXIII,  p.  141. 
Wernicke:   Lehrb.  d.  Psychiatrie,  1900. 


OSTEO-FIBEOMYOMA  OF  THE  UTERUS' 

Sections  from  the  different  pieces  which  were  sent  show  a  variety  of 
tissues. 

Smooth  Muscle. — This  is  present  in  considerable  amount,  although  not 
predominating  in  these  pieces.  It  occurs  especially  around  masses  of  bone, 
and  around  areas  of  soft  connective  tissues;  in  places,  making  a  kind  of 
capsule  for  these  structures.  It  is,  as  usual,  in  irregular  interlacing  bundles, 
and  is  the  seat  of  considerable  hyaline  degeneration. 

Bone. — True  bone  is  present,  showing  bone  corpuscles,  with  canaliculi, 
typical  basement  substance,  lamellae  and  Haversian  canals,  with  marrow 
substance.  The  lamellae  are  arranged  around  the  marrow  spaces  with  more 
or  less  regularity.  Some  of  the  bone  seems  to  be  formed  by  a  direct  meta- 
morphosis of  connective  tissue,  and  is,  therefore,  so-called  osteoid.  But 
there  are  places  which  show  osteoblasts,  forming  bone  in  the  usual  way. 

The  tissue  within  the  marrow  spaces  varies.  It  is  well  supplied  with  blood- 
vessels. In  some  places  it  is  dense,  fibrous  tissue,  in  others  more  delicate 
tissue,  and  in  the  latter  case  may  contain  large  numbers  of  lymphoid  cells. 
Particularly  abundant  in  the  marrow  are  large  cells,  filled  with  granules, 
which  may  be  fine  droplets  of  fat.    Adipose-tissue  cells  occur,  but  are  few. 

Embryonic  Types  of  Connective  Tissue. — There  are  large  areas,  in  some 
pieces  composing  most  of  the  tissue,  of  a  delicately  fibrillated  tissue,  very 
rich  in  cells.  These  cells  are  predominantly  young  connective-tissue  cells, 
but  there  are  also  lymphoid  and  plasma  cells,  and  eosinophiles.  Thin-walled 
blood-vessels  are  fairly  abundant.  This  embryonic  tissue  is  apparently  of 
soft  consistence.  In  addition,  in  connection  ^nth  this  tissue,  and  also  in- 
dependently, are  areas  of  soft  mucoid  tissue,  with  large,  elongated  and 
branching  connective  tissue  cells.  In  one  set  of  sections  this  embryonic 
tissue  occupies  all  except  a  narrow,  peripheral  rim,  which  is  composed  of 
smooth  muscle.    There  are  hyaline  and  necrotic  changes  in  these  tissues. 

Ordinary  Adult  Fibrous  Tissue. — This  is  present  in  connection  with  the 
bone  and  other  tissues. 

Degenerations. — There  are  extensive  areas  of  degeneration:  (a)  Calcifi- 
cation both  of  muscle  and  hyaline  connective  tissue,  (b)  hyaline  and  necrotic 

'Report  on  a  pathological  specimen.    In:    Osteo-Fibromyoma  of  tlie  Uterus,  by 
George  B.  Johnston,  Richmond,  Virginia. 
Am.  Gynaec.  &  Obst.  J.,  N.  Y.,  1901,  XVIII,  307-308. 

432 


OSTEO-FIBROMYOMA  OF  THE  UTERUS  433 

changes  have  affected  considerable  areas,  (c)  actual  disintegration  of  the 
necrotic  areas,  with  fatty  metamorphosis  and  deposit  of  cholesterin  crystals. 

Diagnosis. — Histologically,  Dr.  Randolph's  designation  of  the  tumor  as 
osteo-fibromyoma  is  unobjectionable. 

Remarl-s. — The  tumor  must,  I  think,  be  referred  to  embryonic  remnants, 
and  there  is  no  objection  to  considering  it  as  a  teratoid  formation,  although 
not  a  very  complex  one.  Besides  the  bone  and  smooth  muscle,  there  is  a 
great  deal  of  peculiar  embryonic  connective  tissue  in  the  growth,  partly 
mucoid  in  character,  and  partly  more  cellular,  and  this  tissue  is  quite  unlike 
any  found  in  ordinary  myomatous  tumors. 


MEDULLARY  FOEM  OF  SARCOMA  OF  THE  STERNUM,  WITH 
METASTASES  IX  THE  LYMPHATIC  GLANDS ' 

I  am  indebted  to  Dr.  D.  F.  Unger,  of  Mercersburg,  Pa.,  for  this  specimen. 
I  extract  the  following  points  from  Dr.  Unger's  history  of  the  case : 

Mrs.  S.,  aged  32  years,  weight  120  pounds,  mother  of  three  children,  had 
previously  enjoyed  good  health.  Parents  are  healthy.  On  September  2,  1892, 
she  called  my  attention  to  a  small,  deep  seated,  firm  swelling  just  above  the 
sternal  notch.  This  gradually  increased  in  size.  On  November  30,  1892,  an 
operation  was  performed  by  a  surgeon  in  Philadelphia,  who  regarded  the 
affection  as  a  tubercular  adenitis.  The  operation  consisted  in  curetting  the 
growth  above  the  sternum,  trephining  the  sternum  about  1^  inches  from  the 
top,  curetting  through  this  opening,  passing  a  tube  from  the  upper  to  the 
lower  opening  and  washing  through  this  canal  with  a  solution  of  bichloride 
of  mercury  and  peroxide  of  hydrogen.  Following  this,  the  suprasternal 
growth  increased  in  size  so  as  to  form  an  irregularly  elevated,  somewhat 
nodular  firm  mass  about  6  cm.  in  diameter,  adherent  to  the  skin,  and  involv- 
ing for  a  short  distance  the  tissues  over  the  upper  anterior  surface  of  the 
sternum.  In  the  latter  situation  the  skin  ulcerated  over  a  small  area.  The 
openings  made  by  the  operation  did  not  close  but  became  filled  with  grayish, 
soft  tissue.  Examination  of  the  patient  on  February  1,  1893,  showed  a 
swelling  projecting  about  ^  inch  at  the  right  margin  of  the  sternum,  at  the 
level  of  the  first  and  second  intercostal  spaces.  This  swelling  increased  so  as 
to  touch  the  opening  made  in  the  middle  of  the  sternum  and  to  reach  the 
margin  of  the  suprasternal  tumor.  February  14  were  noticed  several  swollen 
and  somewhat  painful  lymphatic  glands  just  above  the  middle  of  the  right 
clavicle.  After  this  there  developed  enlargement  of  other  cervical  and  of 
axillary  glands,  and  several  nodules  could  be  felt  beneath  the  skin  of  the 
upper  part  of  the  thorax  in  front.  The  right  arm  became  slightly  oedema- 
tous  and  the  veins  over  the  right  shoulder  distended.  Dullness  on  percus- 
sion, and  absence  of  respiratory  sound  over  the  upper  part  of  the  right  side 
of  the  chest  were  determined.  General  itching  of  the  skin  became  a  most 
troublesome  symptom.  The  pulse  became  accelerated,  respirations  increased 
in  frequency,  and  an  irregular  fever  developed,  the  temperature  running 
from  98°  to  103°  F.  A  note  made  on  July  1,  1893,  records  increase  in  the 
number  and  size  of  enlarged  lymphatic  glands  on  both  sides  of  neck  and  in 
the  axillae,  and  the  presence  of  many  nodules  feeling  like  marbles  beneath 
the  skin  of  upper  part  of  the  thorax  on  both  sides.  These  nodules  are  mov- 
able and  not  painful,  except  when  they  first  appear.    Cough  became  trouble- 

^  Report  of  a  case  before  the  Johns  Hopkins  Hospital  Medical  Society,  Decem- 
ber 4,  1893. 

Johns  Hopkins  Hosp.  Bull.,  Bait.,  1893,  IV,  103-105. 

434 


METASTASES  IN  LYMPHATIC  GLANDS  435 

some  only  during  the  last  two  months  of  life,  and  was  attended  with  little 
expectoration.  During  the  last  two  months  of  life  the  pulse  ranged  from 
120  to  130,  the  respiration  from  30  to  45,  and  the  temperature  from  98°  to 
103°.  Urine  diminished  in  amount,  but  Avas  free  from  sugar  and  albumen. 
The  patient  became  weaker  and  weaker  and  more  emaciated,  and  died 
apparently  from  exhaustion  on  September  2,  1893,  just  one  year  from  the 
date  attention  was  called  to  the  first  swelling  above  the  sternum. 

The  autopsy  was  made  by  Dr.  linger,  from  whose  notes  I  extract  the 
following : 

The  anterior  mediastinum  is  occupied  by  a  large,  firm,  irregularly  nodular 
tumor  mass,  so  closely  adherent  to  the  sternum  that  it  is  necessary  to  remove 
most  of  the  tumor  with  the  sternum.  The  tumor  consists  in  part  of  swollen 
and  adherent  lymphatic  glands.  It  presses  upon  the  vena  cava  superior, 
the  arch  of  the  aorta,  the  arteria  innominata,  the  trachea  and  the  base  of  the 
heart,  but  the  caliber  of  these  channels  does  not  seem  to  be  much  diminished. 
The  glands  at  the  bifurcation  of  the  trachea  and  at  the  root  of  the  lungs  are 
also  the  seat  of  new  growth.  The  tumor  on  section  is  grayish  white,  with 
more  opaque  yellowish  white  areas,  which  in  some  places  are  softened  and 
breaking  do^vn. 

The  right  pleural  cavity  contains  4  pints  of  clear  serum,  and  the  left  1  pint 
of  the  same  fluid.  The  right  upper  lobe  is  adherent  to  the  costal  pleura, 
and  is  closely  incorporated  with  the  tumor  behind  the  sternum,  which  seems 
to  have  grown  continuously  into  it.  This  lobe  is  consolidated  throughout 
with  diffuse  and  nodular  masses  resembling  in  structure  the  tumor  and  pre- 
senting areas  of  necrosis.  The  right  middle  lobe  is  filled  with  tumor  nodules 
of  similar  appearance.  The  lower  lobe  is  compressed.  The  left  lung  is 
adherent  only  at  its  upper  part.  In  the  anterior  edge  of  the  left  upper  lol^e 
is  a  separate  tumor  nodule  the  size  of  a  marble.  The  rest  of  the  lung  appears 
normal.  Pericardium  and  heart  normal,  likewise  the  spleen,  liver,  kidneys, 
abdominal  lymphatic  glands.    Inguinal  glands  not  enlarged. 

Dr.  linger  sent  to  me  specimens  from  this  case  removed  at  autopsy.  I 
had  previously,  during  the  life  of  the  patient,  examined  microscopically  a 
small  piece  of  tissue  excised  from  the  suprasternal  tumor  and  found  it  to  be 
a  sarcoma  composed  of  variously  shaped  cells,  including  giant  cells  of  the 
type  found  in  giant-celled  sarcoma. 

The  specimens  from  the  autopsy  were  preserved  in  alcohol,  and  consisted 
of  the  sternum  with  adherent  tumor,  of  parts  of  the  lungs  containing  tumor 
nodules,  of  lymphatic  glands  from  the  mediastinum,  neck  and  axillae,  and 
of  detached  pieces  of  tumor.  For  convenience  of  transportation  the  sternum 
has  been  divided  transversely  through  the  middle  piece.  The  ribs  are 
severed  close  to  the  sternum. 

The  upper  part  of  the  sternum,  consisting  of  the  manubrium  and  adjacent 
half  of  the  gladiolus,  is  covered  posteriorly  by  a  large,  irregular,  adherent, 
firm  tumor  mass,  extending  to  the  upper  margin  of  the  bone  and  laterally  to 


436  SARCOMA  OF  STEENUM 

the  right  4  cm.  beyond  the  margin  of  the  sternum  and  to  the  left  a  little 
beyond  the  margin.  Parts  of  t4iis  tumor  mass  have  been  cut  away.  The 
remaining  part  measures  8  cm.  in  length  from  above  downwards,  7  cm.  later- 
ally and  4  cm.  in  thickness.  The  free  surface  of  the  tumor  is  irregularly 
lobulated.  To  the  right  margin  of  the  tumor  is  attached  a  piece  of  lung 
measuring  4x6x3  cm.,  which  is  completely  invaded  by  the  new  growth  and 
inseparably  incoroporated  with  the  tumor  behind  the  sternum. 

There  is  a  defect  in  the  manubrium  2  cm.  below  the  top  near  the  median 
line.  This  defect,  1  cm.  in  diameter,  is  surrounded  by  bone  to  the  left,  and 
is  continuous  to  the  right,  with  an  outgrowth  of  the  tumor  through  the 
bone.  It  corresponds  to  the  opening  made  during  life  by  the  trephine.  On 
the  anterior  surface  of  the  manubrium  are  two  detached  firm  tumor  nodules, 
the  larger  measuring  2  cm.  in  length  and  8  mm.  in  breadth. 

In  order  to  determine  the  relation  of  the  tumor  to  the  sternum  the  bone 
was  sawed  through  to  the  median  line  and  the  tumor  partly  cut  through  in 
the  same  plane.  This  section  shows  that  the  manubrium  throughout  nearly 
its  whole  extent  is  invaded  by  the  new  growth,  which  has  caused  perhaps 
some  general  enlargement  of  the  bone,  but  has  not  materially  altered  the 
normal  size  and  shape  so  that  from  external  examination  the  extent  of 
involvement  of  the  bone  would  not  be  suspected.  The  manubrium  measures 
0.3  cm.  in  length,  5  cm.  in  width,  and  2.5  cm.  in  thickness  at  the  level  of  the 
clavicular  articulations. 

Throughout  an  area  of  considerable  extent  the  osseous  substance  is  entirely 
replaced  by  a  grayish  white  or  yellowish  white  tissue  of  medium  consistence, 
in  places  rather  soft.  This  area  begins  on  the  posterior  surface  just  below 
the  center  of  the  manubrium  and  extends  downwards  for  2  cm.  Its  verticle 
length  on  the  anterior  surface  of  the  bone  measures  1.5  cm.  It  occupies  over 
this  extent  the  entire  thickness  of  the  right  half  of  the  manubrium,  and  in 
the  left  half  occupies  the  posterior  part  of  the  bone  leaving  bone  substance 
only  in  front  and  on  the  left  margin.  The  hole  made  with  the  trephine,  now 
filled  with  tlie  new  growth,  corresponds  to  the  central  part  of  this  area  in 
which  no  bone  substance  is  present. 

Above  and  below  this  area  of  complete  destruction  of  bone  the  spongy 
texture  of  bone  can  be  made  out,  at  first  very  much  rarefied,  and  gradually 
becoming  near  the  upper  and  lower  ends  of  the  manubrium  more  nearly  nor- 
mal in  arrangement.  The  soft  part  of  the  tumor  replacing  bone  merges 
gradually  into  the  part  where  plates  of  bones  are  present.  Throughout  the 
manubrium  the  marrow  spaces,  much  dilated  near  the  soft  area,  are  filled 
with  grayish  white  tissue  of  the  same  general  appearance  as  that  in  the 
tumor.  This  filling  up  of  the  medullary  spaces  with  new  growth  renders  the 
cancellous  tissues  of  the  mamibrium  markedly  different  in  aspect  from  the 


METASTASES  IN  LYMPHATIC  GLANDS  437 

normal  appearance  in  the  adjacent  middle  piece  of  the  sternum.  The  whole 
manubrium  on  section  has  a  nearly  uniform,  solid,  grayish  white  appearance, 
in  which  the  bony  plates  can  be  more  readily  appreciated  by  the  touch  than 
by  the  eye.  The  cartilage  between  the  first  and  second  pieces  of  the  sternum 
and  the  remainder  of  the  sternum  are  normal. 

The  tumor  on  the  posterior  surface  of  the  sternum  is  directly  continuous 
with  that  part  of  the  new  growth  in  the  manubrium  which  occupies  the  area 
in  which  the  bone  is  entirely  gone.  At  the  upper  and  lower  margins  of  this 
area  the  periosteum  on  the  posterior  surface  of  the  manubrium  can  be  traced 
as  a  grayish  fibrous  band  outwards  over  and  into  the  post-sternal  tumor  for 
a  distance  of  3  to  3  cm.,  giving  the  impression  of  a  growth  from  the  interior 
of  the  bone  pushing  the  periosteum  out  and  then  breaking  through  it. 
Above  and  below  this  apparent  outgrowth  of  the  tumor  from  the  bone  the 
tumor  has  developed  to  the  extent  already  indicated,  and  has  come  into  con- 
tact with  the  periosteum,  from  which,  however,  it  can  be  separated  without 
difficulty. 

To  the  right  of  the  sternum  the  tumor  has  grown  laterally  and  forwards 
so  as  to  fonn  a  projecting  mass  4  cm.  in  width,  filling  the  first  intercostal 
and  part  of  the  second  intercostal  spaces.  This  is  the  swelling  which  was 
recognized  during  life  at  the  upper  part  of  the  right  margin  of  the  sternum. 

Upon  section  the  prevailing  aspect  of  the  tumor  is  firm  and  grayish  white, 
with  some  denser  grayish  fibrous  bands  running  through  it.  In  many  places 
can  be  seen  more  opaque  yellowish  white  areas  of  coagulation  necrosis. 
These  areas  are  irregular  in  size  and  shape,  some  being  5  or  6  mm.  in 
diameter.  In  three  places  these  areas  are  softened  and  broken  down  so  as  to 
form  little  cavities  with  friable,  necrotic  contents  and  irregular  walls. 

The  consolidated  upper  lobe  of  the  right  lung  presents  in  general  a  similar 
appearance,  diffuse  growth  and  circumscribed,  often  coalescing  nodules  of 
grayish  white  firm  tissue,  in  places  necrotic.  The  swollen  lymphatic  glands, 
some  as  large  as  a  pullet's  egg,  and  the  separate  tumor  nodules  over  the 
sternum  are  likewise  of  a  nearly  uniform  grayish  white  color,  with  areas  of 
firm  coagulation  necrosis,  and  in  a  few  places  with  areas  of  broken  down 
necrotic  tissue.  The  pigmented  bronchial  lymphatic  glands  are  similarly 
aft'ected.  In  places  the  new  growth  has  extended  through  the  capsules  of  the 
lymphatic  glands  and  involved  the  surrounding  tissues. 

The  microscopical  examination  reveals  essentially  the  same  structures  in 
the  main  tumor  in  and  attached  to  the  sternum  and  in  the  metastases.  The 
grayish  white,  fresher  parts  of  the  growth  are  composed  of  cells  and  scanty 
stroma.  The  cells  are  of  various  shapes,  small  round  cells  with  deeply 
staining  single  nuclei,  larger  cells  of  an  epithelioid  habitus,  fusiform  cells, 
giant  cells,  and  cells  with  deeply  staining,  large,  irregular  budding  nuclei. 


438  SAECOMA  OF  STERNUM 

such  as  occur  normally  in  the  marrow  of  the  bones.  In  places  one  or  the 
other  of  these  various  forms  of  cells  may  predominate,  but  in  general  they 
are  mixed  together.  The  stroma  is  in  places  scanty,  the  tissue  being  com- 
posed mostly  of  cells ;  in  other  places  it  is  more  abundant,  and  it  may  form 
dense  bands  of  sclerotic  fibrous  tissue  with  few  cells.  There  is  no  regularity 
in  tlie  arrangement  of  the  cells,  especially  no  suggestion  of  an  alveolar 
arrangement.  The  giant  cells  are  present  both  in  the  sternal  tumor  and  in 
the  metastases.  They  are  not  abundant,  but  are  seen  here  and  there  in  all 
of  the  sections.  They  are  large  protoplasmic  bodies  with  large  multiple 
nuclei,  usually  clumped  in  the  central  part  of  the  cell.  None  are  seen  with 
a  mural  arrangement  of  the  nuclei  or  suggestive  of  tubercle  'giant  cells. 
Allied  to  these  giant  cells  are  large  round  and  oval  cells  with  deeply  staining, 
often  very  irregular  large  nuclei,  some  ring-like,  some  like  the  letter  S,  and 
many  budding  (cellules  a  noyau  hourgeonnant).  These  cells  are  abundantly 
present.  Transitional  forms  suggest  the  development  of  the  giant  cells  from 
the  cells  with  the  budding  nuclei.  In  the  more  opaque  yellowish  areas  the 
appearance  is  that  of  typical  coagulation  necrosis,  absence  of  nuclei  or  pres- 
ence of  fragments  of  nuclei.  These  areas  are  usually  dense  and  somewhat 
fibrous  in  appearance,  but,  as  already  mentioned,  some  are  disintegrated  into 
a  structureless  detritus.  The  margins  of  the  necrotic  areas  show  the  same 
structure  as  in  the  rest  of  the  tumor,  or  may  be  more  fibrous  in  texture.  In 
no  places  are  seen  tubercles  of  appearances  indicating  tuberculosis.  Stain- 
ing for  tubercle  bacilli  and  for  other  bacteria  fails  to  show  any  bacteria. 

The  appearances  described  establish  the  diagnosis  of  sarcoma.  The  possi- 
bility that  the  growths  are  syphilitic  was  considered.  The  areas  of  coagula- 
tion necrosis  are  not  unlike  those  which  occur  in  gumma,  but  the  structure 
of  the  surrounding  parts  and  other  clinical  and  anatomical  characters  cannot 
well  be  reconciled  with  the  diagnosis  of  syphilis.  Areas  of  coagulation 
necrosis  of  the  character  present  in  this  specimen  are  not  uncommon  in 
some  kinds  of  sarcoma. 

The  sarcoma  is  of  the  mixed-celled  type  with  cell  elements  belonging  to  the 
marrow  of  the  bones.  Giant  cells  of  this  type  and  large  cells  with  large, 
irregular,  budding  nuclei  occur  more  frequently  in  sarcoma  of  bone  than  in 
any  other  kind  of  sarcoma.  The  relation  of  the  tumor  to  the  manubrium 
sterni  cannot  well  be  explained  otherwise  than  upon  the  supposition  that  the 
tumor  originated  in  this  bone,  a  view  confirmed  by  the  histological  structure. 
The  most  natural  interpretation  is  that  the  tumor  sprang  from  the  marrow 
of  the  bone,  but  tumors  of  similar  structure  may  spring  from  the  periosteum. 
The  relation  of  the  periosteum  to  the  tumor  as  already  described  cannot  be 
considered  conclusive  proof  of  the  central  origin  of  the  tumor,  as  a  similar 
anatomical  arrangement  may  occur  with  primary  tumors  of  the  periosteum 


METASTASES  IN  LYMPHATIC  GLANDS  439 

and  secondary  invasion  of  the  bone.  While  therefore  I  am  inclined  to  the 
view  that  the  growth  originated  in  the  medullary  part  of  the  bone,  I  do  not 
think  that  the  possibility  of  a  periosteal  origin  can  be  positively  excluded. 

There  are  several  points  of  especial  interest  which  suggest  themselves  in 
connection  with  this  case. 

It  is  interesting  that  there  has  been  no  new  production  of  bone  coincident 
with  the  extensive  destruction  of  bone.  This  type  of  sarcoma  in  the  long 
bones  is  likely  to  contain  newly  formed  bone,  but  it  does  not  always,  and 
when  originating  in  the  short  bones  it  is  less  likely  to  do  so. 

The  main  tumor  topographically  belongs  to  the  group  of  tumors  of  the 
anterior  mediastinum,  and  the  present  case  is  one  of  unusual  origin  of  such 
tumors. 

The  extensive  secondary  involvement  of  lymphatic  glands  in  this  case  is  an 
unusual  feature  of  sarcoma.  This  involvement  was  limited  to  the  glands 
within  the  thorax  and  in  the  neck  and  axillae.  At  one  time  during  life 
Hodgkin's  disease  was  suspected.  The  numerous  discrete  nodules  over  the 
sternum  and  thorax  occurred  in  situations  where  there  are  no  preexisting 
lymphatic  glands.  These  metastases  were  probably  of  lymphatic  origin 
and  invaded  the  fasciae  and  muscles,  which  were  replaced  by  the  new  growth. 

Giant  celled  sarcoma  is  ranked  as  a  comparatively  benign  type  of  sarcoma, 
and  is  not  likely  to  metastasize.  The  present  tumor  cannot  be  considered  as 
a  typical  giant  celled  sarcoma  like  the  ordinary  epulis.  The  giant  cells 
were  less  numerous  and  the  rest  of  the  tumor  was  richer  in  cells,  especially 
in  small  round  cells,  than  an  ordinary  epulis.  It  is  however,  a  somewhat 
arbitrary  matter  as  to  what  proportion  of  giant  cells  is  necessary  to  establish 
the  diagnosis  of  giant  celled  sarcoma.  In  the  present  case  the  giant  cells 
Were  of  the  regular  medullary  type,  and  although  not  very  abundant,  they 
were  present  in  fair  number  both  in  the  primary  growth  and  in  the  metas- 
tases. More  numerous  were  the  large  marrow  cells  with  budding  nuclei, 
which  appear  to  merge  into  the  giant  cells.  The  histological  evidence  of 
malignancy,  however,  was  expressed  in  this  case  by  the  abundance  of  such 
cells  as  are  found  in  common  forms  of  rapidly  developing  mixed  celled 
sarcoma. 

The  occurrence  of  the  necrotic  areas  and  the  occasional  disintegration  of 
these  areas  are  not  so  rare  in  sarcoma,  especially  sarcoma  of  the  bones,  as  to 
need  especial  emphasis. 

Several  cases  of  primary  sarcoma  of  the  sternum  have  been  recorded,  and 
nearly  the  whole  sternum  has  been  successfully  excised  for  this  disease,  but 
this  bone  is  not  a  common  seat  of  primary  sarcoma. 


DIFFUSE  INFILTRATING  CARCINOMA  OF  THE  STOMACH* 
I.  Abstract  of  Clinical  History  by  F.  R.  S'^kiiTH 

Dr.  Welch  has  requested  me  to  give  a  brief  history  of  the  case  from  which 
rhe  specimen  came.  The  man  came  into  the  hospital  in  the  beginning  of 
April,  but  had  been  under  observation  in  the  dispensary  sometime  before, 
complaining  of  indigestion,  with  flatulence  and  pyrosis,  which  had  lasted 
for  six  months.  He  absolutely  denied  that  he  had  ever  vomited;  then  he 
corrected  himself  and  said  that  he  did  not  vomit  but  spat  up  a  good  deal 
of  bitter  stuff.  On  asking  him  if  he  ever  vomited  in  large  quantities  he 
said  no. 

The  family  history  of  the  patient  is  negative,  except  that  the  family  fear 
that  his  sister  may  have  a  similar  trouble,  for  which  reason  they  have 
allowed  the  autopsy.  His  personal  history  is  entirely  negative.  He  has  no 
long  history  of  indigestion.  Up  to  four  or  five  months  before  coming  into 
the  hospital  he  had  been  a  thoroughly  healthy  man,  a  very  moderate  drinker, 
and  had  no  venereal  disease  and  had  lived  a  very  regular  life. 

His  occupation,  that  of  a  tailor,  had  been  a  sedentar}'  one.  The  symptoms 
that  he  complained  of  were  slight  pain  in  the  epigastric  region  and  loss  of 
appetite.  When  the  stomach  was  empty  he  complained  more  of  an  uncom- 
fortable feeling  than  of  pain.  The  pain  was  rarely  sharp.  He  went  to 
St.  Joseph's  Hospital  in  December  and  was  treated  he  said,  for  indigestion. 
While  there  he  caught  cold  and  had  a  swollen  gland  under  the  left  clavicle. 
When  he  came  into  the  dispensary  the  epigastric  region  was  examined  and 
nothing  whatever  was  found.  Dr.  Finney  was  asked  to  look  at  this  gland 
in  the  left  axilla,  and  after  examining  it  and  hearing  the  man's  symptoms, 
he  made  the  diagnosis  of  carcinoma  of  the  stomach.  He  was  seen  by 
Dr.  Osier  about  a  fortnight  afterwards.  Dr.  Osier  said  he  felt  something 
indefinite  in  the  epigastric  region  but  he  would  not  positively  say  anything 
about  its  size,  except  that  it  was  probably  a  very  small  lump.  The  man 
came  to  the  dispensary  from  January  to  April.  All  his  symptoms  grew 
worse,  and  he  developed  swollen  glands  under  the  other  clavicle,  and  then 
after  a  few  weeks,  there  was  a  distinct  lump  or  ridge  in  the  epigastric 
region.    This  grew  larger  and  the  patient  became  more  and  more  distressed, 

'  Report  of  a  case  before  the  Johns  Hopkins  Hospital  Medical  Soc,  May  15, 
1893. 

Johns  Hopkins  Hosp.  Bull.,  Bait,  1893,  IV,  98-99. 

440 


INFILTEATING  CAECINOMA  OF  THE  STOMACH         441 

He  came  into  the  hospital  April  4.  The  ridge  was  then  very  distinct  and 
was  found  to  occupy  the  right  hypochondrium  and  expended  as  low  down  as 
the  umhilicus.  The  stomach  tube  was  inserted  and  brought  up  some  blood. 
It  distressed  the  patient  so  very  much  that  it  was  not  tried  again.  Two 
attempts  were  made  to  dilate  his  stomach  with  bicarbonate  of  soda  and 
tartaric  acid.  He  had  hardly  swallowed  the  tartaric  acid  when  he  vomited, 
and  therefore  the  outlining  of  the  stomach  was  always  somewhat  unsatis- 
factory. This  ridge-like  mass  extended,  when  the  stomach  was  distended 
as  well  as  could  be,  slightly  below  the  umbilicus.  It  was  said  in  the  note 
to  feel  something  like  a  rolled-up  omentum.  The  resonance  of  the  tumor 
suggested  that  it  might  be  connected  with  a  cavity.  Dr.  Finney's  diagnosis 
was  confirmed  by  Dr.  Osier.  Although  suffering  some  pain,  the  patient  was 
fairly  comfortable,  but  he  gradually  grew  worse.  The  patient  lost  weight 
very  rapidly  and  the  tumor  increased  in  size.  The  only  other  thing  of 
interest  in  the  case  was  that  one  morning  he  complained  of  great  pain  in 
the  left  leg,  which  was  swollen  and  very  painful  to  the  touch  and  which  made 
him  take  to  his  bed.  The  inguinal  glands  on  that  side  seemed  to  be  enlarged, 
but  no  thrombosis  of  the  vein  could  be  felt.  The  leg  got  better,  but  he 
gradually  sank,  and  at  his  own  desire  he  went  home.  The  same  night  he  was 
taken  very  ill  and  died  in  the  morning. 

II.  Pathological  Eeport 

This  case  was  diagnosed  during  life  as  one  of  carcinoma  of  the  stomach. 
If  it  were  only  that,  perhaps  it  would  not  be  worth  while  to  exhibit  it  here, 
but  it  is  a  form  of  carcinoma  of  the  stomach  not  very  common,  although  you 
will  find  it  described  in  the  literature.  The  interest  of  the  case  is  due  also  to 
the  fact  that  the  disease  can  be  readily  confounded  with  fibrosis  or  cirrhosis 
of  the  stomach,  so  that  the  literature  of  the  subject  of  cirrhosis  of  the 
stomach  is  of  very  little  value  so  far  as  cases  are  reported  as  fibrosis  of  the 
stomach,  induration  of  the  pylorus,  etc.,  without  microscopical  examination. 
In  other  words,  a  large  proportion  of  the  older  cases  to  be  found  in  the 
literature  reported  as  cirrhosis  of  the  stomach  are  in  reality  this  disease, 
viz.,  diffuse  cancer  of  the  stomach.  At  the  autopsy  the  parts  around  the 
stomach  were  the  seat  of  marked  fibroid  induration.  The  transverse  colon, 
the  mesentery,  the  duodenum  and  the  pancreas  were  all  more  or  less  matted 
together.  I  exhibit  here  the  entire  stomach.  You  will  observe  that  the  size 
and  the  shape  of  the  organ  are  about  the  size  and  shape  of  the  kidney.  The 
cavity  of  the  stomach  is  reduced  to  an  extremely  small  capacity.  The  walls 
are  enormously  thickened;  the  mucous  membrane  is  everywhere  intact;  no 
ulceration  and  no  nodular  growth.  It  is  entirely  a  diffuse  disease  involving 
all  of  the  coats  and  all  of  the  parts  of  the  stomach.  The  thickening  is  univer- 
31 


442         INFILTRATING  CAECINOMA  OF  THE  STOMACH 

sal,  but  is  somewhat  ^eater  towards  the  pylorus  than  at  the  fundus.  Exam- 
ining more  carefully,  we  find  that  certain  coats  of  the  stomach  are  very  much 
thickened.  The  grayish,  more  translucent,  muscular  coat  is  extremely 
hypertrophied  and  makes  up  one-third  to  one-half  of  the  entire  thickness 
of  the  walls  of  the  stomach.  The  peritoneum  is  smooth  and  glistening  and 
distinctly  thickened,  but  not  extremely  so.  The  submucous  coat  of  the 
stomach  is  enormously  thickened,  is  extremely  dense  and  fibrous  in  char- 
acter, and  looks  as  though  it  was  the  primary  seat  of  the  disease.  The 
mucous  membrane  is  a  very  thin  line,  and  is  distinctly  atrophied.  The 
firm  consistence  and  unyielding  character  of  the  walls  of  the  stomach  cause 
it  to  remain  open  on  incision.  There  is  nothing  at  all  suggestive  of  a  tumor; 
there  is  no  circumscribed  or  lobulated  new  growth.  Cirrhosis  of  the  stomach 
consists  in  a  fibrous  overgrowth  in  the  walls  without  cancerous  involvement. 
This  condition,  which  cannot  be  distinguished  by  the  naked  eye  from  cir- 
rhosis, is  really  cancerous,  as  determined  by  the  microscope.  The  micro- 
scope shows  the  following  condition  of  things :  The  mucous  membrane  is  an 
extremely  thin  membrane  indeed.  The  tubules  can  be  made  out,  but  they  are 
very  much  altered  in  size  and  broken  up  in  general  arrangement.  You  can 
make  out  rows  of  cells  suggesting  a  tubular  arrangement,  and  that  is  about 
all.  The  muscularis  mucosae  is  extremely  hypertrophied  and  is  everywhere 
provided  with  nests  of  cancer  cells  running  down  in  strands  connecting  the 
mucous  membrane  with  the  submucosa.  The  submucous  coat  is  the  seat  of 
large  cancerous  alveoli.  The  cancer  cells  are  to  be  found  in  all  of  the  coats 
of  the  stomach.  They  are  present  in  the  mucous  membrane  where  they  have 
a  tendency  to  conform  more  or  less  to  the  tubular  arrangement  of  the 
mucous  membrane,  but  they  are  different  from  the  cells  which  belong  nor- 
mally to  the  tubules  of  the  stomach.  Many  of  them  are  very  large,  irregular 
cells,  with  large  deeply  staining  vesicular  nuclei.  Similar  clumps  of  cells 
extend  in  bands  and  alveoli  through  the  muscularis  mucosae,  and  form  the 
largest  masses  in  the  submucosa.  The  alveoli  containing  cancer  cells  extend 
into  the  muscular  coats  along  the  septa  and  between  individual  fibers.  There 
is  no  coat  of  the  stomach  which  has  escaped.  This  is  the  type  of  infiltrating 
cancer  as  distinct  from  the  one  which  grows  in  the  form  of  a  circumscribed 
tumor.  Here  the  infiltration  is  uniform  throughout  the  walls  of  the 
stomach.  This  type  of  cancer  is  found  also  in  the  ovary,  which  is  then  like 
a  very  large  ovary,  the  regular  outlines  being  preserved.  There  is  such  a 
thing  also  as  infiltrating  cancer  and  sarcoma  of  the  serous  membranes,  which 
spread  out  flat  like  a  pancake  and  do  not  form  tumor  masses.  I  have  seen 
one  in  the  meninges  of  the  brain  which  was  simply  a  uniform  thickening, 
preserving  accurately  the  normal  appearances  of  the  dura  mater  so  far  as 
hhape  was  concerned.    We  have  no  positive  information  as  to  which  coat  of 


INFILTEATING  CARCINOMA  OF  THE  STOMACH         443 

the  stomach  is  primarily  involved  in  this  case.  The  general  idea  is  that  the 
^owth  originates  in  the  mucosa.  One  would  almost  be  tempted  to  think 
that  there  was  a  uniform  involvement  of  the  tubules  and  that  everywhere 
they  tended  to  grow  down  through  the  rauscularis  mucosae  and  into  the  sub- 
mucosa.  I  have  alluded  to  this  form  of  carcinoma  in  the  article  in  Pepper's 
System  of  Medicine  on  Cancer  of  the  Stomach  and  called  attention  to  the 
danger  of  confounding  it  with  cirrhosis  of  the  stomach.  The  growth  in  this 
instance  was  primary  in  the  stomach.  The  only  secondary  nodules  present 
are  in  the  neighboring  lymphatic  glands. 

I  was  particularly  interested  in  this  case,  because  some  years  ago  I  made 
an  autopsy  on  a  somewhat  similar  one,  also  a  case  of  diffuse  infiltrating  car- 
cinoma of  the  walls  of  the  stomach,  but  it  was  secondary.  The  woman, 
about  40  years  of  age,  had  double  carcinoma  of  the  ovary,  of  that  form  in 
which  we  have  this  exaggeration  of  the  normal  shape.  There  was  marked 
ascites  in  that  case,  and  the  fluid  was  withdrawn  during  life.  From  the 
character  of  the  fluid  I  ventured  a  diagnosis  of  carcinoma  involving  the 
peritoneum.  No  operation  was  done  in  the  case.  There  was  no  suspicion 
during  life  that  the  stomach  was  involved.  We  found  in  the  stomach  a  uni- 
form enlargement  of  all  the  walls  without  ulceration  of  the  mucous  mem- 
brane, and  with  extreme  narrowing  of  the  lumen  of  the  stomach.  I  have 
placed  under  the  microscope  a  section  of  this  stomach  for  your  inspection. 
The  peritoneal  coat  is  thickened,  the  muscular  coat  considerably  hyper- 
trophied,  and  the  submucous  coat  shows  interlacing  bands  of  fibrous  tissue. 
The  mucous  membrane  in  this  case,  instead  of  being  atrophied,  is  hyper- 
trophied.  There  is  a  marked  lengthening  of  the  gastric  tubules  and  a 
marked  hypertrophy  of  the  muscularis  mucosae  in  this  case.  It  looks  like 
a  diffused  fibroid  induration  of  the  organ,  and  would  correspond  to  descrip- 
tions of  fibroid  induration  of  the  stomach  or  cirrhosis  of  the  stomach.  It, 
however,  contains  nests  of  cancer  cells.  In  this  case  the  involvement  was 
from  the  peritoneum  and  secondary.  The  type  of  the  cancer  was  that  of 
carcinoma  of  the  ovary.  We  have  three  diseases  which  can  produce  gross 
alterations  in  the  stomach,  indistinguishable  from  each  other  to  the  naked 
eye :  cirrhosis  or  fibroid  thickening  of  the  stomacli,  primary  infiltrating  car- 
cinoma of  the  stomach,  and  secondary  infiltrating  carcinoma  of  the  stomach. 


SYRIXGO-CYSTOMA ' 

The  case  is  a  perfectly  typical  one  of  the  Jacquet-Darier  group  of  cases. 
In  general  there  has  been  such  a  remarkable  uniformity  in  the  reported 
cases  referred  to  this  group  that  it  is  quite  improbable  that,  as  claimed  by 
Moller,  some  are  of  endothelial  and  others  of  epithelial  origin.  While  a 
considerable  number  of  authors  (since  the  report  of  the  first  case  by  Kaposi 
in  1868  as  a  lymphangioma)  have  adopted  the  hypothesis  of  endothelial 
origin  (some  as  a  lymphangioendothelioma  and  others  as  haemangioendo- 
thelioma),  I  believe  tliat  the  epithelial  nature  of  the  tumors  has  been  demon- 
strated. 

I  also  believe  that  the  evidence  is  very  strong  that  tumors  of  the  Jacquet- 
Darier  type  originate  from  sweat  ducts  or  the  "  Anlagen  "  of  sweat  ducts. 
It  is  true  that  actual  connection  of  the  epithelial  strands  and  cysts  with 
preexisting  sweat  glands  has  been  missed  by  most  of  the  investigators,  and 
it  may  be  exceptional,  but  there  are  now  several  well  authenticated  reports 
where  such  a  connection  has  been  recognized,  as  for  example  in  cases  reported 
by  Blaschko,  Xeumann,  Joseph  and  Deventer,  Fiocco,  Winkler,  Dohi,  Land- 
stiener  and  IVIatzcnucr,  Stockmann  and  others,  so  that  this  side  of  the  evi- 
dence is  fairly  strong.  Dohi's  observation  is  interesting  of  narrow  epithelial, 
tube-like  connection  of  cysts  with  the  interpapillary  epithelial  processes, 
such  connections  resembling  sweat  ducts  and  being  probably  such.  Then 
weight  is  to  be  given  to  Torok's  argument,  who  made  the  first  thorough 
study  of  the  histogenesis  of  these  tumors,  that  the  absence  or  rare  occurrence 
of  sweat  glands  in  the  area  of  the  tumor,  in  contrast  to  their  presence  in  the 
adjoining  skin,  is  indicative  of  the  transformation  of  preexisting  sweat 
tubules  into  the  tumor  elements. 

I  attach,  however,  even  greater  importance  in  support  of  the  sweat  gland 
theory  of  histogenesis  of  these  tumors  to  the  resemblance  between  the  epi- 
thelial strands,  nests  and  cysts  and  the  tubules  of  sweat  glands,  and  your 
sections  show  this  resemblance  very  well.  There  is  a  manifest  resemblance 
between  the  narrow,  often  wavy  or  twisting  strands  of  epithelium  connected 
with  the  cyst  and  tlio  tubules  of  the  sweat  glands,  but  most  significant,  and 
it  seems  to  me  conclusive,  is  the  presence  in  many  of  the  cysts  and  tubular 

1  Report  on  a  Pathological  specimen  of  R.  L.  Sutton,  Kansas  City,  October  18, 
1911.  [Quoted  in  article  by  R.  L.  Sutton  and  C.  C.  Dennis:  J.  Am.  M.  Ass., 
Chicago.  1912,  LVIII.  333-336.] 

Unpublished. 

444 


SYRINGO-CYSTOMA  445 

strands  of  the  double  row  of  epithelial  cells,  the  outer  row  being  flat  and  the 
inner  row  cubical,  precisely  with  the  arrangement  so  characteristic  of  the 
cellular  lining  of  the  sudoriparous  tubules.  Of  course  this  arrangement  is 
not  in  all  places  apparent  in  consequence  of  the  pressure  of  the  contents  of 
.the  cyst,  of  proliferation  of  cells  and  other  obvious  causes,  but  it  can  be 
recognized  in  so  many  places  that  it  cannot  be  doubted  that  it  is  a  character- 
istic histological  feature  of  this  class  of  tumors.  I  do  not  see  how  this  can 
be  interpreted  otherwise  than  as  evidence  of  the  origin  of  the  tumor  from 
sweat  glands. 

Much  more  problematical,  it  seems  to  me,  is  the  decision  of  the  question  as 
to  whether  the  tumor  springs  from  previously  normal  sweat  ducts  or  from 
congenital  or  acquired  defects  of  the  sweat  glands.  In  favor  of  the  con- 
genital theory  is  the  occurrence  of  so  many  instances  of  the  affection  in 
early  life  and  especially  its  occurrence  in  several  members  of  the  same 
family,  a  point  emphasized  by  many  of  those  who  have  reported  cases,  as 
Quinquad,  Stockmann,  Elschnig,  Gassmann,  Winkler,  Csillag  and  others. 
Of  much  interest  are  Schidachi's  experiments  in  which  he  succeeded  in  pro- 
ducing similar  cysts,  even  with  epithelial  strands,  by  occlusion  of  the  sweat 
ducts. 

Now  as  regards  the  relation  of  these  tumors  of  the  Jacquet-Darier  type,  to 
which  such  a  confusing  multiplicity  of  names  have  been  given,  and  the 
benign  multiple  cystic  epithelioma  of  Brooke  and  Fordyce,  I  am  inclined  to 
hold  them  apart.  I  cannot  weigh  the  value  which  has  been  attached  to  the 
clinical  points,  especially  the  difference  in  location,  but  in  Brooke's  type  of 
tumor  connection  of  the  growth  with  the  epidermis,  with  hair  follicles  and 
outlets  of  sebaceous  glands  is  usually  very  evident. 

In  your  sections  I  see  the  two  cysts  to  which  you  refer  in  your  letter  lying 
close  to  a  sebaceous  gland,  but  I  fail  to  make  out  any  connection  between  the 
two,  and,  so  far  as  I  know,  Hartzell  is  the  only  one  who  claims  to  find  con- 
nection. His  case  is  so  poorly  described  and  the  photographs  so  poor  that  I 
do  not  think  it  can  be  satisfactorily  interpreted.  It  may  be,  as  you  surmise, 
that  it  is  a  combination  of  the  two  types  (Jacquet-Darier  and  Brooke). 
Hartzell  speaks  of  the  tube-like  structures  being  lined  with  cylindrical  epi- 
thelium, and  does  not  seem  aware  of  the  importance  of  the  two  layers  of  cells 
in  the  true  syringo-cystomata. 

In  Brooke's  tumor  the  outer  row  of  cells  is  cylindrical,  whereas  in  the 
Jacquet-Darier  tumor  it  is  flat.  Of  course  the  occurrence  of  colloid  degenera- 
tion in  both  types  of  tumor,  with  the  resulting  cysts,  points  to  analogies, 
which  are  all  the  closer  from  the  fact  that  horn  cysts  have  occasionally  been 
found  in  the  upper  layers  of  syringo-cystoma,  such  keratinisation  being  of 
course  a  marked  feature  of  the  Brooke's  timior,  although,  as  Csillag  has 


446  SYEIXGO-CYSTOMA 

demonstrated,  the  colloid  cysts  and  the  horn  cysts  in  the  benign  cystic  epi- 
thelioma have  not  the  same  origin. 

In  spite,  however,  of  such  apparent  analogies  and  even  transitions  I  hold 
with  the  majority  of  authors  that  syringo-cystoma  is  histogenetically  distinct 
from  benign  cystic  epithelioma,  the  former  originating  from  sweat  tubules, 
either  fully  developed  or  congenital  rest,  and  the  latter  from  the  basal  cells 
of  the  epidennis,  hair  follicles  and  sebaseous  glands. 

As  you  perhaps  know.  Pick  and  some  others  object  to  regarding  the  so- 
called  syringo-cystadenomata  as  true  adenomata,  the  question  being  whether 
there  is  any  thing  of  the  nature  of  a  true  secretion.  If  the  hyaline  or  colloid 
material  in  the  cysts  is  merely  the  result  of  cellular  degeneration  the  propriety 
of  such  names  as  cystoma  or  cyst  adenoma  would  be  questionable,  but  Stock- 
mann  has  apparently  shown  that  in  some  instances  the  cysts  and  tubules 
contain  genuine  secretion,  so  that  I  see  no  particular  objection  to  calling  the 
Jacquet-Darier  tumor  a  syringoma,  or  syringo-cystoma,  or  hydrocystoma  or 
the  like.  Still  strictly  speaking  it  is  a  benign  cystic  epithelioma,  although 
the  latter  name  had  better  be  reserved  for  the  Brooke-Fordyce  type  of  tumor. 

I  have  found  Stockmann's  article  in  the  "  Archiv  fiir  Dermatologie  und 
Syphilis,"  1908,  Bd.  XCII,  Hft.  I,  a  good  one.  You  will  find  there  refer- 
ences to  Schidachi's  experiments  and  other  authors  to  whom  I  have  referred. 


CHEOiSriC  JAUNDICE  WITH  XANTHOMA  MULTIPLEX ' 

I  hope  that  a  careful  histological  study  will  be  made  of  specimens  of  the 
xanthomatous  lesions  in  this  case,  as  the  subject  is  one  offering  many  un- 
solved problems.  My  attention  was  directed  a  few  years  ago  to  xanthoma 
through  the  opportunity  of  examining  sections  sent  to  me  by  Dr.  Pollitzer  of 
New  York,  whose  specimens  were  utilized  by  Unna  in  his  description  of  gen- 
eralized xanthoma.  The  specimens  which  I  examined  were  of  ordinary 
xanthoma  palpebrarum.  There  appear  to  be  at  least  three,  and  probably 
more,  clinical  types  of  disease  which  have  been  called  xanthelasma  or  xan- 
thoma, namely,  xanthoma  vulgare  of  the  eye  lids,  an  extremely  common  and 
unimportant  affection,  juvenile  xanthoma  multiplex,  and  generalized  xan- 
thoma of  adults,  most  frequently  secondary  to  jaundice  and  diabetes  mellitus, 
but  occurring  also  without  any  apparent  cause.  Unna  makes  a  sharp  his- 
tological difference  between  the  common  form  of  palpebral  xanthoma  and 
generalized  xanthoma.  According  to  him,  in  the  former  the  fat,  which  gives 
the  yellow  color  to  the  lesion,  is  of  a  peculiar  character  and  lies  in  extra- 
cellular masses  within  the  lymphatic  spaces  and  vessels,  there  being  no  true 
xanthoma  cells.  I  am  not  aware  that  Unna's  views,  which  are  not  in  accord- 
ance with  those  usually  accepted,  have  been  confirmed.  Waldeyer  in  his  first 
publication  and  most  other  investigators  following  him  find  the  fat  in  small 
granules  or  droplets  within  large  cells  believed  to  be  derived  from  connective 
tissue  cells  or  endothelial  cells,  these  fatty  cells  being  the  so-called  xanthoma 
cells.  Later  Waldeyer  suggested  that  these  cells  may  come  from  his  plasma 
cells  or  Toldt's  embryonic  fat  forming  cells,  and  this  view  has  had  a  number 
of  advocates.  Dr.  Pollitzer  finds  evidence  in  his  sections  of  palpebral  xan- 
thoma that  the  characteristic  cells  containing  fat  are  derived  from  striped 
muscle,  partly  displaced  through  congenital  abnormality  into  the  corium. 
VIrchow  objects  to  the  designation  "  Xanthelasma  "  or  "  Xanthoma,"  as  not 
based  upon  histological  characters,  and  has  proposed,  as  a  substitute,  fibroma 
lipomatodes,  but  this  suggestion  seems  to  have  met  with  little  success.  There 
is  a  rare  form  of  lipoma  which  bears  considerable  anatomical  resemblance  to 
certain  of  the  larger  neoplasms  which  have  been  described  as  xanthomata.  I 
examined  such  a  specimen  some  years  ago.    It  was  a  lobulated  and  encapsu- 

^  Remarks  on  a  case  of  Dr.  Osier  and  report  of  pathological  specimen,  before 
the  Johns  Hopkins  Hospital  Medical  Society,  February  4,  1901. 
Johns  Hopkins  Hosp.  Bull.,  Bait.,  1901,  XII,  220-221. 

447 


448  XANTHOMA  MULTIPLEX 

lated  subcutaneous  tumor,  the  size  of  a  hen's  egg,  removed  from  the  groin 
of  a  young  man,  and  believed  at  the  operation  to  be  an  ordinary  lipoma.  On 
section  it  presented  a  uniform,  yellow  surface,  and  microscopically  it  was 
composed  entirely  of  vascular  stroma  and  large  cells  filled  with  minute 
granules  or  droplets  of  fat.  After  removal  of  the  fat  single,  or  occasionally 
multiple,  round  or  oval  nuclei  with  nucleoli  were  found  usually  about  the 
middle  of  cells  filled  with  a  finely  porous  or  reticulated  protoplasm.  There 
was  a  stroma  around  individual  cells  or  groups  of  cells.  I  interpreted  the 
tumor  as  composed  of  embryonic  adipose  tissue.  There  were  no  adult  adi- 
pose-tissue cells  with  single,  large  oil  drops.  I  mention  this  tumor  on  account 
of  its  histological  resemblance  to  certain  xanthomatous  tumors,  but  other- 
wise it  has  no  relation  to  xanthoma,  as  it  was  the  only  new  growth  and  was 
in  the  subcutaneous  tissue.  It  is  highly  probable  that  a  variety  of  distinct 
affections  have  been  described  under  tlie  name  of  xanthoma. 


CHRONIC  PERITONITIS  WITH  COMPLETE  OBSTRUCTION, 
CAUSED  BY  NUMEROUS  CONSTRICTIONS  OF  A  PRE- 
VIOUSLY UNDESCRIBED  CHARACTER,  THROUGHOUT  THE 
INTESTINE ' 

I.  Abstract  of  Clinical  History  by  Miles  F.  Porter 

History. — Dr.  L.  A.  H.,  aged  35,  married,  had  an  attack  of  pneumonia  21 
years  previously,  followed  by  empyema  for  which  a  rib  was  resected  and 
drainage  instituted.  Complete  recovery  followed,  but  the  diseased  chest 
still  remained  considerably  contracted.  He  drank  excessively  throughout 
1903,  but  now  is  a  total  abstainer.  In  December,  1906  (six  months  before 
admission),  after  a  full  meal  of  sausage,  he  was  taken  with  very  severe 
abdominal  cramps  and  vomiting,  for  relief  from  which  he  took  f  grain  of 
morphine  hypodermically.  The  pain  was  worse  in  the  lower  abdomen,  and 
especially  on  the  right  side,  and  some  tenderness,  localized  over  the  painful 
area,  followed.  This  attack  caused  him  to  quit  work  for  one  day.  Six  weeks 
later  he  had  a  similar  attack,  accompanied  by  vomiting  of  a  light,  bright 
green-colored  fluid  and  a  more  severe  one  followed  on  March  28,  1907.  The 
bowels  were  constipated.  A  few  days  before  coming  to  the  hospital  he  had 
a  formed  putty-colored  stool.  No  elevation  of  temperature  was  present  dur- 
ing these  attacks.  The  patient  stated  that  his  abdomen  was  sore  when  he  was 
jolted ;  he  complained  of  accumulation  of  gas  in  the  stom.ach,  which  was  re- 
lieved by  belching  or  the  use  of  the  stomach  pump.  He  frequently  vomited 
bright  green-colored  fluid  and  complained  of  a  metallic  taste  in  the  mouth. 
It  was  very  difficult  to  get  the  bowels  to  move ;  the  stools  were  not  formed. 

Examination. — The  patient  was  a  fairly  well  nourished  man  of  good  color, 
and  of  dark  complexion.  His  abdomen  was  rather  retracted  and  boogy.  An 
indistinct  mass  was  felt  in  the  pelvic  region,  both  on  rectal  and  on  abdominal 
palpation.  Examination  of  the  chest  was  negative.  The  pulse  was  62 ;  the 
temperature,  97.6°  F.  The  blood  picture  was  normal.  The  urine  was  normal 
in  character  but  reduced  in  amount,  only  18  ounces  being  passed  in  the  24 
hours.  Bacteriological  examination  of  the  vomitus  showed  a  bacillus  which 
culturally  and  microscopically  gave  characteristics  of  Bacillus  typhosus. 
The  Widal  reaction  was  positive.    There  was  no  reaction  to  two  injections 

^  Report  on  a  specimen  of  Miles  F.  Porter,  August  14,  1907. 
J.  Am.  M.  Ass.,  Chicago,  1908,  LI,  719-722. 

449 


450  CHRONIC  PERITONITIS 

of  old  tuberculin  of  5  and  10  mg.,  respectively.  Permeability  of  the  intes- 
tinal tube  was  demonstrated  by  the  charcoal  test.  No  clinical  diagnosis  could 
be  made  other  than  that  of  a  low  grade,  wide-spread  peritonitis  with  incom- 
plete obstruction  of  the  bowels. 

Operation. — An  exploratory  laparotomy  with  the  patient  under  ether 
anaesthesia  was  done  two  days  after  admission  to  the  hospital.  Practically 
universal  close  adhesions  were  found  between  contiguous  bowel  surfaces. 
There  was  some  fluid.  Very  little  adhesion  between  the  visceral  and  the 
parietal  peritoneum  was  found.  The  appendix  was  freed  and  removed,  but 
presented  nothing  abnormal.  The  bowel  adhesions  were  fairly  completely 
broken  up.  The  small  intestine  seemed  abnormally  short  and  nowhere  con- 
stricted, but  on  the  contrary  unusually  large  in  its  transverse  diameter,  and 
on  palpation  felt  as  though  it  were  filled  with  angle  worms.  Attempts  to 
empty  sections  of  the  bowel  by  stripping  were  ineffectual.  The  surface  of 
the  bowel  was  grayish  white,  and  the  non-adherent  surfaces  perfectly  smooth. 
An  incision  was  made  into  the  ileum.  There  was  no  escape  of  faeces  or  gas. 
The  bowel  seemed  full  of  mucous  membrane  arranged  in  accordion-like  folds. 
A  probe  could  not  be  made  to  pass  in  either  direction ;  but  the  finger  could 
be  made  to  pass  in  either  direction  by  carefully  working  the  folds  aside. 
It  was  concluded  that  the  case  was  hopeless,  even  temporary  relief  being  out 
of  the  question.  The  incisions  in  the  ileum  and  the  abdominal  wall  were 
closed. 

Just  previous  to  the  operation  the  patient's  pulse  was  70,  and  temperature 
97.6°  F.  Twelve  hours  after  the  operation  his  pulse  was  102  and  his  tempera- 
ture 98.2°  F.  Sixteen  hours  after  the  operation  a  catheter  was  inserted  and 
the  bladder  found  empty.  Only  eight  ounces  of  urine  were  secreted  during 
the  three  days  that  intervened  from  the  time  of  operation  until  his  death. 
Tliere  was  no  vomiting  for  20  hours  after  the  operation,  when  it  commenced 
again  and  continued  until  death.  At  first  the  vomitus  was  green,  but  later 
became  dark  brown  in  color.  The  temperature  gradually  rose  to  102°  F., 
while  the  pulse  rate  increased  and  became  more  feeble  in  quality,  and  death 
occurred  from  a  gradual  failure,  72  hours  after  operation. 

Autopsy. — About  two  hours'  time  intervened  between  the  time  of  death 
and  the  autopsy.  Both  the  wound  in  the  abdomen  and  that  in  the  intestine 
were  found  to  be  healing  normally.  There  was  no  evidence  of  recent  peri- 
toneal infection.  Tbe  stomach  presented  nothing  abnormal  except  some 
adliesions  to  the  abdominal  wall.  The  whole  of  the  small  intestine  and  all  of 
the  large  intestine  except  the  rectum  were  covered  by  a  layer  of  grayish  white, 
ratber  strong,  plastic  material  about  -j^  of  an  inch  in  thickness,  whicli  could 
be  stripped  off,  leaving  tlie  underlying  peritoneum  looking,  to  the  naked  eye, 
normal.    This  membrane  was  smooth  on  the  free  surfaces  of  tlie  bowel  but 


WITH  COMPLETE  OBSTRUCTION  451 

ragged  where  it  had  been  adherent.  The  adventitious  coat  did  not  reduce  the 
transverse  diameter  of  the  bowel,  but  shortened  it  by  actual  measurement  by 
70  to  80  per  cent.  Closely  placed  parallel  incisions  around  the  bowel  would 
allow  it  to  be  drawn  out  to  its  normal  length,  as  would  stripping  off  the 
false  membrane.  Mesenter}'  and  omentum  were  normal.  The  liver,  spleen, 
and  peritoneal  surface  of  the  bladder  were  covered,  as  were  the  bowels,  by 
this  membrane,  but  not  diminished  in  size.  Transverse  section  of  the  bowel 
shows  its  lumen  to  be  occluded  by  transverse  folds  of  mucous  membrane. 

II.  Pathological  Repoet 

Gross  Appearances. — The  specimen,  which  had  been  preserved  in  for- 
malin and  alcohol,  was  a  portion  of  the  small  intestine,  evidently  jejunum, 
which  had  been  severed  from  the  mesenteric  attachment  except  at  one  end, 
where  a  small  piece  of  the  mesentery  was  retained. 

The  specimen  measured  21  cm.  in  length  opposite  to  the  mesenteric 
border,  and  15  cm.  in  length  along  the  mesenteric  border.  For  a  distance  of 
13  cm.  from  one  end  the  intestine  had  been  cut  open  along  the  mesenteric 
margin,  the  remaining  8  cm.  being  unopened.  The  unopened  part  of  the 
intestine  measured  10  cm.  in  external  circumference,  was  not  collapsed  and 
felt  from  the  outside  as  if  filled  with  a  rather  elastic  and  moderately  firm 
material.  The  transverse  section  presented  by  the  cut  end  of  this  solid, 
unopened  part  of  the  intestine  showed  no  recognizable  lumen,  but  in  its 
place  a  complicated  mass  of  folded  mucous  membrane.  Only  with  difficulty 
and  after  much  twisting  and  turning  could  a  metallic  probe  be  passed 
from  the  lumen  corresponding  to  the  opened  part  of  the  intestine  through 
the  lumen  of  the  unopened  part;  after  inserting  the  probe  this  latter  part 
was  cut  open  opposite  to  the  mesenteric  attachment,  when  it  was  seen  that 
the  obstruction  was  due  entirely  to  the  infoldings  of  the  intestinal  wall 
occurring  at  short  intervals  and  kept  in  place  by  an  organized  false  mem- 
brane attached  to  the  peritoneal  surface.  This  false  membrane  covered  the 
entire  peritoneal  surface  of  the  intestine,  but  over  the  opened  part  of  the 
specimen,  as  stated  in  Dr.  Porter's  letter  accompanying  the  specimen, 
"  closely  placed  parallel  incisions  around  the  gut,  made  through  the  false 
membrane,"  had  permitted  this  part  of  the  intestine  to  be  stretched  to  its 
normal  length  and  had  effaced  the  involutions  of  the  intestinal  wall,  so  that 
here  the  lumen  was  free  from  obstruction  and  the  mucous  surface  showed 
no  especial  abnormality.  It  was  evident  that  by  a  similar  procedure  the 
same  result  could  be  obtained  in  the  remaining  part  of  the  specimen.  There 
were  no  contents  found  in  the  lumen  of  the  obstructed  intestine  after  open- 
ing it  as  described. 


453  CHRONIC  PEEITONITIS 

As  has  already  been  stated,  the  entire  peritoneal  surface  of  the  intestine 
was  covered  with  a  false  membrane.  This  membrane,  which  was  from 
0.5  to  1  mm.  in  thickness,  was  grayish  in  color,  of  firm  consistence,  almost 
cartilaginous  in  translucence  over  most  of  its  extent  and  smooth  over  the 
greater  part  of  its  free  surface,  although  careful  inspection  showed  that 
much  of  this  surface  was  finely  granular  or  slightly  shaggy,  as  would  result 
from  a  thin  coating  of  fibrous  exudate  on  an  organized  fibrous  membrane. 
No  remnants  of  fibrous  threads  or  bands  projected  from  the  free  surface  of 
the  false  membrane.  This  dense  and  nearly  uniform  false  membrane,  con- 
sisting apparently  of  organized  fibrous  tissue  with  superficial  fibrinous 
exudate,  was  attached  to  the  underlying  wall  of  the  intestine  by  fi])rillated 
connective  tissue,  which  was  evidently  also  of  new  formation.  This  attach- 
ment was  in  general  so  loose  that  there  was  no  difficulty  in  peeling  the  dense 
false  membrane  off  from  the  intestine,  the  surface  thus  exposed  appearing 
smooth  in  consequence  of  the  delicacy  of  the  severed  threads  of  tissue.  The 
attachment  of  the  false  membrane  was  firmer  and  more  intimate  over  the 
intestine  situated  between  the  infoldings  of  the  wall,  while  it  was  very 
loosely  attached  directly  over  these  infoldings.  No  tubercles  could  be  seen 
with  the  naked  eye  in  the  outer  covering  of  the  intestine  or  elsewhere. 

In  this  examination  the  greatest  interest  attached  to  the  infoldings  of  the 
intestinal  wall  which  have  filled  up  and  obstructed  the  lumen  of  the  bowel. 
As  these  infoldings  had  been  entirely  obliterated  in  the  opened  part  of  the 
intestine  by  numerous  transverse  incisions  through  the  false  membrane  they 
could  be  studied  only  in  the  8  cm.  of  the  intestine  which  had  not  been  cut 
open  previous  to  the  reception  of  the  specimen.  The  folds  were  the  result  of 
a  sharp  bending  inward  of  all  the  coats  of  the  intestinal  wall  from  a  direc- 
tion parallel  to  the  long  axis  of  the  intestine  to  one  perpendicular  to  this 
axis,  much  as  if  a  contraction  of  a  narrow  band  of  the  circular  muscular  coat 
had  occurred  and  persisted  or  been  held  in  place.  These  segmental,  trans- 
verse constrictions  of  the  intestinal  wall  followed  each  other  longitudinally 
at  short  intervals,  as  many  as  eight  being  present  in  a  length  of  8  cm.  of 
intestine.  Each  of  the  infoldings  extended  as  a  rule  transversely  nearly 
around  the  circumference  of  the  intestine,  but  some  were  shorter.  Tliere  was 
a  certain  alternating  arrangement  of  the  folds  such  that  the  shallower  part 
of  one  fold  fitted  in  between  the  deeper  parts  of  adjacent  folds,  whereby  a 
spiral-like  arrangement  of  the  intestinal  ridges  on  the  mucous  surface 
resulted.  This  arrangement  suggested  that  each  infolding  corresponded  to 
the  course  of  the  larger  vessels  which  run  transversely  round  the  bowel,  and 
in  many  of  the  folds  it  was  possible  to  see  these  vessels  in  the  lax  tissues 
bridging  the  depressions.  The  depth  of  the  folds  averaged  from  1  to  2  cm., 
the  tendency  was  for  each  fold  to  become  shallower  in  its  course  and  to  dis- 


WITH  COMPLETE  OBSTRUCTION  453 

appear  before  it  had  completely  encircled  the  bowel.  The  thickness  of  the 
folds  was  about  1  cm.,  the  adjacent  muscular  coats  on  each  side  of  a  fold 
being  nearly  in  apposition  in  the  deeper  part  of  the  depression  and  separating 
slightly  above,  so  as  to  approximate  a  Y-shape.  Between  successive  folds  the 
lumen  appeared  of  nonnal  dimensions,  but  this  lumen  was  evident  only  on 
stretching  the  intestine  longitudinally  as  the  folds  were  so  close  together  and 
so  deep  as  to  obstruct  it  completely.  The  dense  false  membrane  which  cov- 
ered the  outer  surface  of  the  intestine  did  not  follow  the  involution  of  the 
intestinal  coats  into  the  folds,  but  it  extended  bridge-like  over  the  depres- 
sions, and  it  was  evident  that  it  was  these  bridges  of  false  membrane  which 
kept  the  folds  in  place.  By  incising  these  bridges  transversely  over  the  folds 
the  latter  were  readily  obliterated  on  stretching  the  bowel  longitudinally. 
There  was  little  evidence  of  the  constrictions  on  inspection  of  the  outer  wall 
of  the  unopened  intestine,  which  appeared  merely  invested  in  a  uniform 
grayish  coat  of  false  membrane;  still,  careful  inspection  showed  frequent 
slight  external  furrows  corresponding  to  the  constrictions.  The  delicate 
loose  connective  tissue  already  noted  as  present  beneath  the  denser  part  of 
the  false  membrane  was,  however,  present  in  the  depressions,  stretching  be- 
tween the  adjacent  sides  of  an  infolding.  It  was  evident  that  the  existence  of 
the  constrictions  or  folds  described  must  have  caused  an  extraordinary  short- 
ening of  the  intestine.  By  actual  measurement  of  the  part  of  the  intestine 
in  which  the  constrictions  were  in  place  (not  having  been  obliterated  by 
transverse  cuts  through  the  false  membrane)  there  was  found  to  be  a  short- 
ening of  from  70  to  80  per  cent  of  the  normal  length.  The  inner  or  mucous 
surface  of  the  intestine  showed  no  abnormalities  other  than  the  ridges  re- 
sulting from  the  constrictions.  Vulvulae  conniventes  were  high  and  numer- 
ous as  in  the  jejunum.  There  was  no  ulceration,  necrosis  or  haemorrhage 
to  be  detected  with  the  naked  eye.  The  small  tag  of  mesentery  which  still 
remained  attached  to  one  end  of  the  intestine  was  moderately  rich  in  adipose 
tissue  and  contained  two  or  three  small  lymphatic  glands,  free  from  any 
abnormality. 

Microscopical  Examinations. — The  mucous  membrane  was  well  preserved 
and  appeared  entirely  normal.  The  submucosa  also  was  free  from  any  patho- 
logical change.  The  circular  muscular  coat  appeared  somewhat  thicker  in 
the  part  of  the  intestinal  wall  included  in  the  constrictions  than  in  that 
between  these,  but  this  was  probably  due  to  the  obliquity  of  the  section  of 
the  muscle  in  the  former  situation.  The  spaces  between  the  muscular 
bundles  of  the  circular  coat  appeared  rather  wider  than  normal.  The  longi- 
tudinal muscular  coat  also  appeared  somewhat  thicker  near  and  in  the  de- 
pressions, but  the  same  explanation  probably  applies  here  also.  The  coat  wa5 
in  places  moderately  invaded  by  new  connective  tissue  extending  in  from  the 


454  CHRONIC  PERITONITIS 

peritoneal  surface.  The  existence  of  the  constrictions  was  sharply  defined 
on  the  microscopical  sections  by  abrupt  change  of  the  direction  of  the 
mucous,  submucous  and  muscular  coats,  the  angle  of  the  bend  being  almost  a 
right  angle,  but  with  its  apex  rounded  off.  The  distance  between  the  muscu- 
lar coats  on  each  side  was  about  2  or  3  mm.  at  the  angle  and  became  less  as 
they  approached  the  point  of  union  of  the  muscle  at  the  bottom  of  the  con- 
striction. The  peritoneum  was  entirely  replaced  by  organizing  exudate  and 
connective  tissue.  The  original  subperitoneal  tissue  could  be  made  out  as 
a  layer  firmly  connected  with  the  longitudinal  muscle.  Over  this  was,  first, 
a  layer  of  richly  vascularizing  fibrillated  connective  tissue,  containing  many 
fibroblasts,  plasma  cells  and  lymphocytes.  This  layer  was  very  lax,  with 
wide  meshes  and  numerous  blood  vessels  over  and  between  the  layers  of  the 
infoldings  of  the  subjacent  coats,  whereas  it  was  denser  and  more  intimately 
connected  with  the  adjacent  tissues  between  the  successive  constrictions. 
This  layer  passed  gradually  into  a  dense  layer  of  organizing  connective 
tissue  of  a  rather  sclerotic  or,  in  places,  hyaline  appearance,  containing 
fibers  and  long  fibroblasts,  disposed  mostly  parallel  to  the  longitudinal  axis 
of  the  intestine,  leucocytes  and  developing  capillaries.  In  this  layer,  old 
fibrin  in  process  of  substitution  by  connective  tissue  was  enclosed.  On  the 
free  surface  was  a  fibrinous  exudate,  in  places  old,  dense  and  hyaline  in  char- 
acter, and  in  other  places  fresh  with  fibrillated  fibrin  and  many  polymorpho- 
nuclear leucocytes,  with  fragmenting  nuclei.  The  layer  described  under  the 
gross  appearances  as  "  false  membrane  "  consisted  mainly  of  the  organizing 
connective  tissue  and  exudate.  Corresponding  to  the  constrictions  in  the 
intestinal  wall  the  denser  part  of  the  organizing  exudate  stretched  across  the 
interval  between  the  walls  of  a  fold,  and  did  not  follow  the  intestinal  wall  as 
if  bent  abruptly  inward.  The  subjacent  delicately  fibrillated,  very  vascular, 
lax,  newly  formed  connective  tissue  extended  down  in  long  threads  which 
appeared  to  be  stretched  and  which  ran  perpendicularly  from  the  under  sur- 
face of  the  dense  membrane  into  the  depressions,  which  were  thus  occupied 
by  this  lax  tissue  with  wide  meshes.  Corresponding  to  the  tops  of  many  of 
the  constrictions  the  denser  texture  of  the  bridges  of  false  membrane 
extended  do^vn  for  perhaps  3  or  4  mm.  as  a  wedge-shaped  mass  from  the 
under  surface  of  a  bridge  into  the  depression,  the  apex  of  the  wedge  lying 
in  the  center  of  a  depression.  No  tubercles  were  seen  in  any  of  the  sections. 
Sections  stained  for  bacteria  (for  tubercule  bacilli,  Gram's  stain,  and 
methylene  blue)  showed  various  bacilli  and  cocci  on  the  surface  of  the  exu- 
date, but  these  resembled  bacteria  found  on  the  surface  of  the  mucous  mem- 
brane, and  were  ])robably  the  result  of  postmortem  contamination. 

Pathological  Diagnosis. — Chronic  organizing  peritonitis  of  unrecognized 
etiology.    Intestinal  obstruction  resulting  from  numerous  transverse  infold- 


WITH  COMPLETE  OBSTEUCTION  455 

ings  or  constrictions  of  the  intestinal  wall,  these  being  held  in  place  by 
bridges  of  dense,  organizing  false  membrane. 

Interpretation  of  Findings. — After  completing  the  foregoing  examination 
and  description  I  received  from  Dr.  Porter  two  other  parts  of  the  intestine 
from  the  same  case.  These  were  both  of  small  intestine.  One  measured 
48  cm.  in  length,  and  the  folds  had  been  largely  obliterated  by  transverse 
cuts  through  the  false  membrane.  The  other  piece  was  still  unopened.  The 
appearances  and  pathological  changes  in  these  parts  were  identical  with 
those  already  described,  the  same  obstruction  from  infoldings  of  the  intesti- 
nal wall  existing  as  in  the  specimen  already  described. 

The  mode  of  production  of  intestinal  obstruction  in  this  case  is  most 
remarkable  and  quite  unfamiliar  to  me,  and,  so  far  as  I  am  aware,  pre- 
viously unrecorded,  although  I  have  not  searched  the  literature.  The  peri- 
tonitis was  of  the  organizing,  proliferative  type,  associated  with  fibrinous 
exudation.  It  was  probably  the  primary  lesion.  Anatomical  features  of 
interest  relating  to  the  peritonitis  were  the  uniformity  of  the  false  membrane 
enveloping  the  bowel,  the  absence  of  fibrous  adhesions  to  any  notable  extent, 
the  laxity  of  the  layer  of  connective  tissue  connecting  the  dense  false  mem- 
brane with  the  intestinal  wall  where  the  constrictions  occurred,  and  the 
bridging  of  the  tops  of  the  constrictions  by  the  dense  false  membrane  of  such 
a  nature  that  when  these  bridges  were  cut  through  around  the  bowel  the  con- 
strictions could  be  completely  obliterated  and  the  intestine  restored  to  its 
normal  length  and  appearance,  save  for  the  evidences  of  peritonitis.  Most 
remarkable  were  the  extent  of  intestine,  implicated  in  this  unusual  form  of 
intestinal  obstruction,  all  of  that  submitted  for  examination  being  similarly 
affected,  the  great  shortening  of  the  intestine  in  length  resulting  from  the 
myriads  of  transverse  constrictions,  and  the  symmetry  and  regularity  of  the 
segmental  constrictions  entirely  unlike  the  nicks  and  puckerings  of  the 
intestinal  wall  resulting  from  peritoneal  adhesions. 

It  is  evident  from  the  description  that  the  dense  false  membrane  was 
responsible  for  keeping  the  constrictions  in  place.  A  further  question  is 
whether  it  was  also  responsible  for  their  original  production.  If  it  be  as- 
sumed that  in  process  of  organization  of  a  progressive  fibrinous  exudate  a 
false  membrane,  composed  partly  of  connective  tissue,  was  formed,  that  this 
surrounded  the  bowel  uniformly,  and  was  firmly  adherent  around  the  bowel 
at  intervals,  then  it  would  seem  that  contraction  of  this  false  membrane  in  a 
longitudinal  direction  in  consequence  of  the  growth  of  cicatricial  tissue 
would  draw  the  intestinal  wall  into  transverse  folds  at  the  situations  where 
the  contracting  membrane  is  loosely  attached.  Mr.  Brodel,  who  contributed 
the  drawings,  has  called  my  attention  to  the  possibility  of  explaining  such  a 
disposition  of  the  false  membrane  and  the  situation  and  regularity  of  the 


456  CHROmC  PERITONITIS 

constrictions  by  taking  into  account  the  arrangement  of  the  intestinal  vessels. 
On  an  injected  and  moderately  distended  small  intestine  slight  transverse 
furrows  can  be  seen,  each  corresponding  to  the  course  of  the  artery  which 
passes  from  the  mesenteric  border  over  the  side  of  the  intestine,  these  arteries 
alternating  as  they  pass  now  to  one,  now  to  the  other,  side  of  the  intestine. 

As  already  noted,  the  constrictions  seemed  to  correspond  to  the  situation 
of  these  arteries.  The  suggestion  is  advanced,  therefore,  that  the  situations 
where  the  false  membrane  was  loosely  attached  and  where,  therefore,  the 
constrictions  occurred,  correspond  to  these  arterial  furrows,  and  that  the 
constrictions  themselves  were  due  to  contraction  in  a  longitudinal  direction 
of  the  organizing  false  membrane  which  was  firmly  adherent  to  the  intestinal 
wall  between  the  furrows.  The  distinguishing  feature  of  the  process  in 
accordance  with  this  view  and  as  seems  supported  by  the  histological  charac- 
ters described,  is  the  peculiar  mode  of  organization  of  a  peritoneal  exudate 
whereby  the  resulting  membrane  is  firmly  adherent  in  places  to  the  intestinal 
wall  and  only  loosely  adherent  in  intervening  places.  As  already  noted,  the 
fibers  and  fibroblasts  in  the  organizing  membrane  had  a  prevailing  direction 
parallel  to  the  long  axis  of  the  intestine,  and  this  arrangement  may  account 
for  preponderance  of  contraction  in  this  direction. 

The  mechanical  explanation  which  is  offered  is  advanced  as  an  hypothesis 
without  strong  proof.  Other  hypotheses  have  suggested  themselves  which 
take  into  account  the  participation  of  muscular  contraction  during  life  in 
producing  the  constrictions.  In  the  stage  of  chronic  peritonitis  represented 
in  this  case,  at  which  the  acute  exudate  is  far  removed  by  intervening  newly 
formed  connective  tissue  from  the  muscular  coats,  there  is  no  reason  to 
.assume  paralysis  of  these  coats  during  life. 

While  it  is  apparent  that  the  anatomical  condition  in  this  case  was  in  no 
sense  intussusception,  the  possibility  may  be  entertained  that  muscular  con- 
tractions causing  the  bowel  contractions  may  have  been  such  as  would 
initiate  intussusception,  but  that  the  dense  false  membrane  covering  the 
intestine  was  an  obstacle  to  the  production  of  actual  intussusception. 

Nothing  was  found  to  indicate  the  cause  of  the  peritonitis  by  examination 
of  the  specimen  sent  me. 


Unopened  piece  of  gut,  envelojicd  in  a  faKc  menibrane.  The  shallow  circular 
furrows  on  the  surface  are  located  at  the  region  of  the  infolding  of  the  gut  wall. 
The  cut  end  of  the  gut  shows  the  lumen  practically  obliterated  by  folds  of 
intestinal  mucous  membrane.  A  probe  forced  through  the  folds  demonstrates 
the  difficulty  of  locating  the  lumen. 


Intestine  opened  longitudinally,  showing  infoldings  (a)  of  the  intestinal  wall  (b),  occurring  at  short  intervals  and  kept  in 
place  by  an  organized  false  membrane  (e),  attached  to  the  peritoneal  surface.  On  the  right,  the  intestinal  wall  (6)  has  been 
unfolded  to  its  normal  length  by  cutting  the  false  membrane   (c).     The  brackets  indicate  the  extent  of  unfolding. 


IDIOPATHIC  PHLEGMONOUS  GASTEITIS  ^ 

I  recall  a  case  of  diffuse  phlegmonous  gastritis  which  I  examined  at  autopsy 
several  years  ago  at  Bellevue  Hospital,  New  York.  The  patient  was  a  man 
beyond  middle  life,  with  a  history  of  chronic  alcoholism.  Abdominal  pain, 
vomiting,  and  fever  were  among  the  symptoms,  the  diagnosis  during  life 
being  acute  peritonitis.  The  walls  of  the  stomach  were  nearly  one  centimetre 
in  thickness  and  were  diffusely  affected,  although  the  pyloric  region  was  the 
most  thickened.  The  thickening  was  most  marked  in  the  submucosa,  which 
presented  a  yellowish-white,  rather  firm  appearance.  There  was  no  tumor 
or  large  ulceration,  but  small  drops  of  pus  could  be  squeezed  in  many  places 
from  the  surface  of  the  mucosa  as  through  a  sieve,  and  also  from  the  incised 
wall  of  the  stomach.    There  was  diffuse  seropurulent  peritonitis. 

The  microscope  showed  an  immense  diffuse  infiltration  of  the  submucous 
coat  with  leucocytes,  chiefly  polymorphonuclear.  In  scattered  foci  were 
small  submucous  ahscesses.  Lines  of  pus  cells  extended  up  between  the  gas- 
tric tubules  and  opened  upon  the  free  surface.  The  accumulation  of  pus  cells 
was  most  abundant  in  the  inner  layers  of  the  submucosa  near  the  muscularis 
mucosae  but  the  outer  layers  were  also  infiltrated,  and  strands  of  pus  cells 
extended  through  the  muscular  coats,  the  intermuscular  and  subserous  layers 
of  connective  tissue  being  considerably  thickened  by  purulent  infiltration. 
The  peritonitis  appeared  to  be  secondary  to  the  phlegmonous  gastritis.  I 
did  not  at  the  time  of  the  autopsy  examine  for  the  presence  of  bacteria,  but  1 
have  since  done  so,  and  have  been  able  to  discover  in  the  microscopical  section 
numerous  streptococci. 

Phlegmonous  gastritis  was  described  by  Brinton  under  the  peculiar  name 
of  "  suppurative  linitis,"  and  I  recall  that  in  my  student  days  we  were  ex- 
pected to  know  about  it  under  this  latter  designation, 

^  Report  of  a  case,  during  remarks  on  a  paper  of  Francis  P.  Kinnicutt,  before 
the  Association  of  American  Physicians,  Washington,  D.  C,  May  1,  1900. 
Tr.  Ass.  Am.  Physicians,  Phila.,  1900,  XV,  133. 


457 


THE  EFFUSION  OF  CHYLE  AND  OF  CHYLE-LIKE  MILKY, 
FATTY,  AND  OILY  FLUIDS  INTO  THE  SEROUS 
CAVITIES ' 

I  have  brought  with  me  and  here  present  a  specimen  of  the  fluid  from  a 
case  of  chylous  ascites.  The  specimen  was  recently  sent  for  my  examination 
by  Dr.  McNamara,  of  New  York,  who  has  at  different  times  withdrawn  by 
tapping  several  quarts  of  similar  fluid,  exactly  like  milk  in  its  optical  proper- 
ties, from  the  abdominal  cavity.  The  patient  is  a  boy,  whose  clinical  history 
does  not  render  clear  the  cause  of  the  affection. 

Save  here  and  there  a  stray  leucocyte  or  red  blood  corpuscle,  the  only 
morphological  elements  to  be  seen  microscopically  in  the  fluid  are  extremely 
minute  granules,  so  minute  that  they  cannot  be  recognized  as  fatty  globules. 
This  granular  matter  can  be  dissolved  in  ether,  and  on  evaporating  the  ether 
drops  of  oil  remain.    No  filaria  are  present. 

Those  who  will  look  through  the  literature  relating  to  chylous  effusions, 
will  perhaps  be  surprised  to  find  that  the  pathology  of  the  affection  is  in- 
volved in  considerable  doubt  and  differences  of  opinion.  Quincke  advanced 
the  subject  by  distinguishing  clearly  between  chylous  and  fatty  hydrops,  a 
distinction  of  much  importance,  although  often  lost  sight  of.  The  micro- 
scope enables  us  to  distinguish  between  these  two  affections,  as  in  fatty 
hydrops  there  are  larger  oil  globules,  and  also  fatty  granular  corpuscles  and 
h-mphoid  and  other  cells  in  various  stages  of  fatty  degeneration. 

There  are  many  -wTiters  who  entirely  reject  the  view  that  the  chyle-like 
effusions  in  the  peritoneal  and  the  pleural  cavities  are  due  to  the  escape  of 
chyle  from  the  chyle  vessels.  They  argue  that  in  such  cases  postmortem 
examination  has  not  furnished  satisfactory  demonstration  of  the  existence 
before  death  of  rupture  of  chyle-containing  vessels,  that  the  chemical  con- 
stitution of  the  fluid  differs  in  some  respects  from  that  of  chyle,  notably  in 
the  absence  of  sugar,  and  that  similar  effusions  are  to  be  found  in  parts  of 
the  body  where  no  chyle-containing  vessels  exist. 

Notwithstanding  these  objections,  it  seems  to  me  to  have  been  demon- 
strated that  the  cbyle-like  effusions  in  the  serous  cavities  of  the  abdomen 

^  Presentation  of  specimen  and  remarks  on  a  paper  of  Samuel  C.  Busey,  before 
the  Association  of  American  Physicians,  Army  Medical  Museum,  Washington, 
D.  C,  September  18,  1889. 

Tr.  Ass.  Am.  Physicians,  Phila.,  1889,  IV,  102. 

458 


EFFUSION  OF  CHYLE-LIKE  FLUIDS  459 

and  chest  are  in  reality  the  result  of  the  escape  of  chyle  by  rupture  of  the 
lacteal  vessels  or  of  the  thoracic  duct.  In  many  instances  cancerous  and 
tuberculous  masses  obstructing  large  numbers  of  the  lacteals  at  the  root  of 
the  mesentery  have  been  found,  with  plain  evidences  of  damming  back  of 
chyle  and  rupture  of  lacteal  vessels.  I  do  not  think  that  the  mere  occlusion 
of  the  thoracic  duct,  still  less  obstruction  to  the  venous  flow  in  the  subclavian 
veins,  is  followed  by  serious  interference  with  the  flow  of  lymph  or  chyle.  I 
have  found  the  thoracic  duct  completely  occluded  by  a  tuberculous  throm- 
bus in  a  case  of  acute  miliary  tuberculosis,  without  any  such  effect.  Straus 
has  shown  in  his  interesting  paper  that  the  ingestion  of  substances  like  butter, 
which  are  absorbed  by  the  lacteals,  causes  a  corresponding  change  in  the 
composition  of  the  chylous  effusion.  In  Whitla's  case  the  guarantee  that  the 
perforation  found  in  the  thoracic  duct  occurred  during  life,  is  furnished  by 
the  character  of  the  hole  and  by  the  dissection  of  the  skillful  anatomist, 
Eedfem. 


CATHETERIZATION  OF  THE  URETERS  IN  THE  MALE' 

I  recall  a  case  in  New  York  in  which  I  made  an  autopsy — a  case  in  which 
a  serious  mistake  was  made  which  would  have  been  avoided  had  this  method 
of  determining  the  presence  or  absence  of  the  kidneys  been  used.  The 
patient  was  a  vigorous  young  German  girl  who  had  atresia  of  the  vagina.  An 
effort  had  been  made  to  reach  the  uterus  by  cutting  through  this  closed  va- 
gina. They  opened  tlie  canal  up  to  a  certain  distance  and  then  abandoned  the 
attempt.  Then  they  found  a  mythical  tumor  on  the  left  side.  Various 
diagnoses  were  made  as  to  the  nature  of  that  tumor.  The  prevailing  opinion 
was  that  it  was  connected  with  the  left  ovary,  and,  indeed,  that  was  the 
opinion  of  one  of  the  most  distinguished  surgeons  of  New  York.  Dr.  Lusk, 
who  saw  the  case,  made  a  correct  diagnosis  of  movable  kidney.  The  case 
was  operated  upon  before  the  class  at  Bellevue  Hospital  and  the  kidney 
removed.  There  was  nothing  the  matter  with  the  kidney  other  than  it  was . 
movable.  The  kidney  was  brought  at  once  over  to  my  laboratory.  It  was  a 
very  large,  succulent  kidney.  I  happened  to  have  made  an  autopsy  a  few 
days  before  on  a  man  who  had  only  one  kidney,  and  the  appearance  of  the 
kidney  was  impressed  upon  my  mind;  the  thick  cortex  and  the  beautiful 
markings  of  the  cortex,  the  normal  structure  greatly  exaggerated  but  per- 
fectly healthy.  This  kidney  looked  so  much  like  the  one  just  mentioned  that 
I  surmised  at  once  that  it  was  the  only  kidney  the  patient  had  and  suggested 
that,  to  the  horror  of  the  surgeon.  The  patient  lived  11  to  13  days,  voiding 
no  urine.  For  7  or  8  days  there  were  no  symptoms  to  occasion  alarm.  Dur- 
ing the  last  48  hours  uraemic  symptoms  manifested  themselves  and  the  pa- 
tient died.  The  autopsy  showed  that  the  patient  had  but  one  kidney,  and 
that  had  been  removed  by  the  surgeon.  The  operator  was  very  frank  in  bring- 
ing the  case  to  the  notice  of  the  medical  profession  and  published  it  in  all  its 
details  in  one  of  the  medical  journals  in  1881  or  1882.  He  discussed  at  that 
time  all  the  methods  that  his  ingenuity  could  suggest  as  to  the  possibility  of 
recognizing  the  presence  of  a  second  kidney.  I  do  not  know  that  he  at  that 
time  even  thought  of  the  possibility  of  catheterizing  the  ureter.  I  remember 
that  he  discussed  the  advisability  of  pressing  on  the  ureter  on  one  side  and 
determining  in  that  way  wliether  the  other  was  present.  This  is  simply 
one  case  which  shows  that  there  is  a  practical  use  for  this  procedure. 

'  Remarks  on  a  paper  of  James  Brown,  before  the  Johns  Hopkins  Hospital 
Medical  Society,  Baltimore,  December  17,  1894. 
Johns  Hopkins  Hosp.  Bull.,  Bait,  1895,  VI,  16. 

460 


PEIMAEY  ECHINOCOCCUS  CYSTS'  OF  THE  PLEURA ' 

I  have  examined  the  sections  of  the  cysts.  I  am  of  the  opinion  that  the 
cysts  are  degenerated  echinococcus  cysts.  The  gross  appearances  of  the 
specimens  which  you  showed  me  were  like  those  of  echinococcus  cysts.  The 
microscopical  characters  of  the  fresh  teased  material  and  of  sections  of  the 
hardened  specimens  seem  to  be  best  explained  upon  the  assumption  that  the 
cysts  are  much  degenerated  hydatids.  Cholesterin  crystals  and  fatty  de- 
tritus, such  as  were  present  in  these  cysts,  are  common  in  degenerated 
hydatids.  No  organized  tissue  is  present  in  the  walls  of  the  cysts.  These 
walls,  as  shown  in  the  sections,  present  an  outer,  thin,  hyaline  membrane, 
with  irregular  inner  surface  continuous  with  fragments  and  shreds  of  a 
structureless  material  which  occupies  a  considerable  part  of  the  interior  of 
the  cysts  on  the  sections.  There  are  scarcely  any  intact  cells  in  the  sections : 
here  and  there  a  few  are  attached  to  the  outer  wall  and  a  few  nuclear  frag- 
ments are  seen  in  the  interior,  but  there  is  nothing  indicative  of  suppura- 
tion, or  of  previously  organized  tissue,  nor  is  there  any  suggestion  of  fibrin 
or  inflammatory  exudate  in  the  sections. 

As  no  booklets  can  be  detected,  I  have  looked  carefully  for  the  character- 
istic lamellation  of  the  cuticular  layer  of  echinococcus  cysts.  I  think  that 
there  are  suggestions  of  such  lamellation  in  the  parallel  striae  occasionally 
seen  in  some  of  the  more  coherent  and  hyaline  membranous  fragments 
attached  to  the  wall  and  in  the  interior  of  the  cysts,  but  they  are  not  so  dis- 
tinct as  to  be  convincing. 

It  is  well  known  that  echinococcus  cysts  may  perish  and  undergo  com- 
plete disintegration.  Davaine,.  Leuckart,  Neisser  and  others  have  described 
such  degenerative  changes  in  the  dead  cysts.  In  some  of  these  cases  nothing 
but  the  booklets  remain  to  establish  the  diagnosis.  Sterile  echinococcus 
cysts  occur,  and  should  these  undergo  similar  degeneration,  it  is  evident  that 
not  even  hooklets  would  be  present  to  aid  in  the  diagnosis. 

*  Pathological  report  taken  from  a  letter  to  Charles  Gary  and  Irving  P.  Lyon 
and  published. 

In:  Primary  Echinococcus  Cysts  of  the  Pleura.  Report  of  a  Case  of  Primary 
Exogenous  Echinococcus  Cysts  of  the  Pleura,  Showing  Hyaline  Degeneration  of 
the  Cuticle  without  Lamellation,  with  Notes  from  the  Literature,  by  Charles  Cary 
and  Irving  P.  Lyon. 

Tr.  Ass.  Am.  Physicians,  Phila.,  1900,  XV,  371-373. 

461 


463  PEIMARY  ECHINOCOCCUS  CYSTS  OF  PLEURA 

In  your  case  the  degeneration  has  not  reached  a  stage  in  which  the  gross 
appearances  of  echinococcus  cysts  have  been  obliterated,  but  the  character- 
istic physical  and  microscopical  features  do  not  seem  to  me  reconcilable  with 
any  other  sort  of  cysts  than  much  degenerated  echinococcus  cysts.  As 
already  mentioned,  the  large  amount  of  fatty  detritus  and  of  cholesterin  crys- 
tals within  the  cysts  is  in  favor  of  the  diagnosis  of  degenerated  hydatids. 

Echinococcus  cysts,  of  course,  receive  their  nourishment  from  the  tissues 
in  which  they  are  embedded,  and  impairment  of  this  nutrition  tends  to  the 
production  of  sterility  and  degeneration  of  the  cysts.  In  your  case  the 
partial  and  small  attachment  of  the  cysts  to  the  pleural  membrane  must 
have  favored  these  results  of  imperfect  nutrition,  and  in  this  way  I  should 
explain  at  least  in  part,  the  sterility  of  the  cysts  and  their  degenerated  con- 
dition (April  1,  1900). 

In  my  previous  letter  I  did  not  speak  particularly  of  the  outward  curling 
of  incised  echinococcus  cysts.  This  physical  property  is  well  known,  and  is 
demonstrable  readily  in  fresh,  undegenerated  cysts.  As  it  depends  upon  the 
integrity  of  the  parasite,  it,  of  course,  is  likely  to  disappear  after  the  parasite 
dies  and  undergoes  degeneration,  as  certainly  occurred  in  your  case,  assum- 
ing it  to  be  a  bladder-worm.  It  would  not  be  contended,  of  course,  that  the 
absence  of  this  property  would  exclude  the  diagnosis  of  a  degenerated 
echinococcus  cyst. 

As  I  wrote  you,  I  attach  more  importance  in  explaining  the  sterility  of 
the  cysts,  and  the  evidence  of  death  and  degeneration  of  the  parasite,  to  the 
comparatively  limited  attachment  of  the  cysts  to  the  surrounding  living 
structures,  and  their  consequent  feeble  nutrition  Most  of  the  instances  of 
pleural  echinococci  have  been  of  single  or  few  large  cysts,  firmly  attached 
in  their  circumference.  The  topographical  relations  of  the  cysts  in  your 
case  are  rather  peculiar  and  unusual  (April  5,  1900) . 


MALAEIA ' 
Definition 

Malaria  comprises  the  diseases  caused  by  the  specific  protozoan  parasite 
called  Haematozoon  malariae. 

The  name  "  malaria,"  derived  from  the  Italian  maV  aria  and  signifying 
"  bad  air/'  was  applied  originally  to  the  miasm  or  poison  which  was  sup- 
posed to  produce  the  disease.  It  is  now  used  to  designate  the  disease  itself, 
and  is  the  most  convenient  term  for  this  purpose. 

The  most  characteristic  malarial  manifestations  are  intermittent  or  remit- 
tent fever,  certain  forms  of  the  disease  described  as  "  pernicious,"  and  a 
chronic  cachexia  with  enlarged  spleen  and  anaemia.  The  parasite  discovered 
by  Laveran  is  invariably  present  in  malaria  and  produces  from  the  haemo- 
globin of  the  red  blood  corpuscles  the  brown  or  black  pigment  granules  which 
are  characteristic  of  the  disease. 

Synonyms 

Malarial  fever;  Intermittent  fever;  Chills  and  Fever;  Fever  and  Ague; 
Paludism  or  Paludal  fever;  Swamp  or  Marsh  fever;  Miasmatic  fever; 
Periodical  fever;  Autumnal  fever. 

Names  derived  from  localities  where  the  disease  has  prevailed  with  especial 
intensity  have  sometimes  been  used;  as,  Walcheren  fever,  Batavia  fever, 
Hungarian  fever,  African  fever,  Panama  fever,  Chagres  fever. 

Special  names  have  been  applied  to  certain  types  or  manifestations  of 
malaria ;  as,  remittent  fever,  bilious  remittent  fever,  hemorrhagic  remittent 
fever,  congestive  fever,  dump  ague,  black-water  fever,  black  jaundice. 

History 

There  are  few  diseases  which  can  be  traced  so  surely  and  continuously  as 
malaria  in  medical  writings  from  ancient  times  to  the  present.  Various 
types  of  malarial  fever  are  described  by  Hippocrates,  Celsus,  Galen,  and 
other  ancient  Avriters,  although  it  is  often  impossible  to  determine  the  pre- 
cise characters  of  many  of  the  fevers  described  by  these  authors. 

Celsus  and  Galen  divide  intermittent  fevers  into  quotidian,  tertian,  quar- 
tan, semi-tertian,  and  irregular.  They  recognized  intermittent  fevers  with 
long  intervals.     The  nature  of  their  semi-tertian  fever  (hemitritaeus)  has 

» In:    Syst.  Pract.  M.  (Loomis),  N.  Y.  &  Phila.,  1897,  I,  17-154. 

463 


464  MALARIA 

given  rise  to  much  discussion.  Certain  forms  of  intermittent  fever  were 
believed  by  Galen  to  have  their  seat  in  the  spleen,  others  in  the  liver.  The 
influence  of  marsh  effluvia  and  of  seasons  of  the  year  in  the  causation  of  cer- 
tain of  these  fevers  was  recognized.  Various  symptoms  were  discriminated 
as  to  their  prognostic  significance,  often  with  much  acuteness  of  observation. 
A  passage  in  Celsus  clearly  alludes  to  the  type  of  malarial  fever  now  called 
aestivo-autumnal  fever. 

The  Arabian  physician  Ehazes  described  the  so-called  subintrant  malarial 
fevers.  No  important  advance  beyond  the  knowledge  of  Celsus  and  of  Galen 
concerning  malarial  fevers  was  made  until  toward  the  end  of  the  sixteenth 
century,  when  Mercatus  in  his  work  on  malignant  fevers  described  various 
forms  of  pernicious  paroxysms  in  association  with  intermittent  fever,  par- 
ticularly with  the  tertian  type. 

The  introduction  of  cinchona  bark  from  Peru  into  Europe  by  the  Countess 
del  Chinchon  and  her  body-physician,  Juan  del  Vego,  in  1640,  gave  great 
impetus  to  the  study  of  malarial  fevers,  and,  indeed,  in  its  revolutionizing 
influence  upon  medical  doctrines  this  event  marks  an  epoch  in  the  history  of 
medicine. 

In  the  latter  half  of  the  seventeenth  and  the  beginning  of  the  eighteenth 
century  there  appeared  a  voluminous  literature  regarding  malarial  fevers. 
The  most  notable  of  the  works  upon  this  subject  of  this  period  are  those  of 
Sydenham,  Kichard  Morton,  Torti,  llamazzini,  and  Lancisi.  These  works 
remain  to  this  day  the  great  classics  upon  malaria.  They  contain  the  funda- 
mental clinical  and  therapeutical  facts  and  many  etiological  data  relating  to 
this  disease.  Morton  and  Lancisi  demonstrated  clearly  the  relation  of 
malaria  to  marsh  miasm.  Sydenham  pointed  out  the  differences  between 
vernal  and  autumnal  intermittent  fevers.  Especially  complete  and  keen 
in  analysis  is  the  nosography  of  Torti,^  whose  classification  of  the  malarial 
fevers,  particularly  of  the  pernicious  and  mixed  forms,  has  been  followed 
by  most  subsequent  authors.  The  diagnostic  as  well  as  the  therapeutic  value 
of  the  preparations  of  Peruvian  bark  was  recognized,  and  assisted  materially 
in  the  discrimination  of  the  malarial  fevers  from  the  other  so-called  essen- 
tial fevers.  It  is  interesting  to  note  the  relative  accuracy  of  diagnosis  and 
of  description  of  the  group  of  malarial  fevers  from  the  latter  half  of  the 
seventeenth  century  onward,  in  contrast  to  the  confusion  which  existed  re- 
garding the  other  essential  fevers  until  the  discrimination  of  the  latter  by 
the  pathological-anatomical  studies  of  the  present  century. 

The  military  and  colonial  enterprises  of  England  in  the  eighteenth  century 
served  to  extend  the  knowledge  of  the  geographical  distribution  of  malaria, 

'Torti:  Therapeutlce  specialis  ad  febres  quasdam  perniciosas,  etc.,  Mutinae, 
1712. 


MALAEIA  465 

particularly  in  tropical  climates,  the  works  of  Pringle  and  of  Lind  contain- 
ing especially  noteworthy  observations  on  this  point.  But  the  great  mass  of 
the  very  extensive  literature  on  the  epidemiography  of  malarial  diseases 
which  has  been  so  industriously  collected  and  ably  analyzed  by  Hirsch '  be- 
longs to  the  present  century. 

The  significance,  as  regards  malaria,  of  the  active  studies  in  morbid  an- 
atomy of  the  first  half  of  the  present  century  relates  to  the  clear  differentia- 
tion of  typhoid  fever  from  malarial  and  other  fevers  rather  than  to  the  actual 
contributions  to  the  pathology  of  malaria,  although  these  were  not  lacking. 
The  occurrence  of  enlarged  spleens,  so-called  fever  cakes  or  ague  cakes,  and 
even  the  dark  color  of  the  organs  in  association  with  malarial  fevers,  had 
been  occasionally  observed  by  the  older  writers,  notably  by  Lancisi,  but  the 
intimate  relation  of  these  alterations  to  malaria  was  not  established  until 
during  the  first  half  of  the  present  century. 

Audouard  (1808,  1812,  1818)  emphasized  congestion  and  enlargement 
of  the  spleen  as  the  essential  anatomical  lesion  of  malarial  fever.  Bailly 
(1825)  noted  in  a  series  of  autopsies  on  cases  of  pernicious  malarial  fever 
observed  in  Eome  in  1822  the  dark  color  of  the  cortical  gray  matter  of  the 
brain  and  the  congestion  of  the  cerebral  meninges  and  substance.  He  laid 
especial  emphasis  upon  evidences  of  supposed  inflammation  of  the  central 
nervous  system  and  of  the  stomach  and  intestine.  These  anatomical  obser- 
vations, together  with  those  of  Nepple  (1828,  1835),  and,  to  a  less  extent, 
of  Maillot  (1835),  were  interpreted  in  favor  of  Broussaisism,  which  at  this 
period  exerted  such  a  pernicious  influence  upon  medical  practice. 

Valuable  contributions  to  the  pathological  anatomy  of  malarial  fevers, 
especially  of  the  remittent  type,  were  made  in  the  United  States  during  the 
fourth  decade  of  this  century  by  Stewardson  in  Philadelphia,  Swett  in  New 
York,  and  Anderson  and  Frick  in  Baltimore.  Stewardson  demonstrated  the 
bronzed  color  of  the  liver  in  remittent  fevers,  and  regarded  this  as  the  char- 
acteristic anatomical  criterion  of  the  disease.  His  observations  were  con- 
firmed and  extended  by  the  other  writers  named.  Alonzo  Clark  in  1855 
demonstrated  that  the  bronzed  color  of  these  livers  is  due  to  the  presence  of 
granules  of  yellow,  brown,  and  black  pigment,  which  he  regarded  as  derived 
from  the  coloring  matter  of  red  blood-corpuscles.  The  monumental  work  of 
Daniel  Drake  on  "  The  Principal  Diseases  of  the  Interior  Valley  of  North 
America"  (1850,  1854)  contains  a  large  amount  of  valuable  information, 
based  upon  personal  observation  and  research,  as  to  the  distribution  and 
characters  of  the  malarial  fevers  in  the  then  Western  States  of  this  country. 

In  the  light  of  recent  discoveries  it  is  interesting  to  note  the  ingenious 
arguments  advanced  by  John  K.  Mitchell  in  his  work  "  On  the  Cryptogamous 

^Hirsch:    Handbuch  der  historisch-geographischen  Pathologie,  Stuttgart,  1881. 


466  MALARIA 

Origin  of  Malarious  and  Epidemic  Fevers,"  published  in  1849,  in  favor  of 
the  doctrine  of  contagium  animatum.  This  book  deserves  to  rank  with  the 
more  frequently  quoted  work  of  Heule  relating  to  the  same  line  of  argument. 
At  about  the  same  period  Bassi  and  Easori  in  Italy  also  advocated  the  para- 
sitic theory  of  malaria. 

The  discoverer  of  the  malarial  pigment  is  Heinrich  Meckel,  who  found  and 
described  the  pigment  in  1848  in  the  blood  and  organs  of  the  dead  body  of 
an  insane  patient.  He  was,  however,  ignorant  of  the  relation  of  this  pigment 
to  malaria.  The  next  report  concerning  the  pigment  was  in  1849  by  Virchow, 
who  observed  it  in  the  body  of  a  man  who  had  suffered  from  chronic  malaria. 
There  soon  followed  the  observations  of  Heschl,  Planer,  A.  Clark,  Tigri, 
Frerichs,  and  others,  fully  establishing  the  relation  of  the  pigment  to  malaria. 
The  source  of  the  pigment  was  regarded  by  Meckel  and  Virchow  as  in  the 
spleen,  and  this  doctrine  was  elaborated  by  Frerichs.  Planer  (1854)  was 
the  first  who  saw  the  pigment  in  the  fresh  blood  of  living  patients,  and  he 
suggested  that  the  pigment  may  be  formed  in  the  circulating  blood — a  view 
which  was  more  fully  presented  and  advocated  by  Arnstein  (1874)  and  by 
Kelsch  (1875). 

There  is  no  doubt  that  some  of  the  pigmented  bodies  which  are  now  recog- 
nized as  parasitic  organisms  had  been  seen  by  earlier  observers  without 
knowledge  of  their  true  nature.  Thus  Meckel  noted  the  presence  of  pigment 
granules  in  colorless,  hyaline  bodies  devoid  of  definite  nuclei.  He,  and  more 
particularly  Virchow  and  Frerichs,  observed  pigment  in  fusiform  and  curved 
bodies  in  the  blood,  which,  although  interpreted  as  endothelial  cells  of  splenic 
origin,  in  all  probability  were,  at  least  in  part,  the  crescentic  forms  of  the 
parasite.  Some  of  the  larger  pigmented  spherical  organisms  must  have  been 
seen  and  mistaken  for  pigmented  leucocytes. 

In  Xovember,  1880,  Laveran  discovered  the  parasitic  nature  of  these  and 
previously  unrecognized  forms  in  the  blood  of  malarial  patients,  and  thereby 
introduced  a  new  era  into  our  knowledge  of  the  malarial  diseases. 

The  discover}'  of  the  malarial  parasite  has  furnished  an  unfailing  means 
of  diagnosis  of  malarial  diseases,  has  materially  advanced  our  knowledge 
of  their  pathology,  has  led  to  a  better  understanding  of  their  clinical  phe- 
nomena and  various  types,  has  furnished  important  data  for  prognosis,  and 
has  led  to  improvements  in  methods  of  treatment.* 

*  The  so-called  Bacillus  malariae  described  in  1879  by  Klebs  and  Tommasi- 
Crudeli,  which  for  a  short  period  had  a  certain  vogue,  chiefly  with  Italian  writers, 
never  rested  upon  satisfactory  observations  which  indicated  that  it  bore  any 
relation  to  malaria,  and  it  deserves  no  more  consideration  than  the  palmella  of 
Salisbury  and  the  other  alleged  malarial  organisms  described  before  Laveran's 
discovery. 


MALARIA  467 

Paeasitology 
historical 

In  1879,  A.  Laveran,  a  French  militar}'  surgeon,  stationed  at  the  time  in 
the  province  of  Constantine,  Algeria,  began  to  study  the  pathological  anatomy 
of  malaria,  and  at  once  directed  his  attention  to  the  much  discussed  question 
of  the  origin  of  the  pigment.  He  observed  in  the  blood  of  malarial  patients 
certain  pigmented  bodies  different  from  the  melaniferous  leucocytes,  but  he 
was  uncertain  as  to  their  nature  until,  on  November  6,  1880,  he  discovered 
that  some  of  these  pigmented  bodies  threw  out  long  flagella  endowed  with 
such  active  lashing  movements  as  to  convince  him,  as  they  have  convinced 
every  one  who  has  since  then  seen  them,  that  they  are  living  parasites. 
Laveran  published  his  observations  in  a  note  to  the  Academic  de  Medecine 
in  Paris,  presented  November  23,  1880.  This  was  followed  by  the  publica- 
tion of  several  notes  in  1880  and  1881,  and  in  the  latter  year  appeared  a  small 
monograph  by  Laveran  on  the  parasitic  nature  of  malaria." 

In  these  various  early  publications  Laveran  describes  (1)  pigmented  cres- 
centic  and  ovoid  bodies;  (2)  spherical,  transparent  bodies,  sometimes  free, 
sometimes  applied  to  the  surface  of  red  blood  corpuscles,  the  smallest  about 
one-sixth  of  the  diameter  of  a  red  blood  corpuscle  and  containing  only  one  or 
two  fine  pigment  granules,  these  representing  an  early  stage  of  development 
of  (3)  larger,  pigmented,  spherical  bodies  averaging  6 /x  in  diameter,  but 
sometimes  larger  than  a  red  blood  corpuscle,  and  containing  numerous,  often 
moving,  pigment  granules;  (i)  bodies  similar  to  the  last  mentioned,  but 
beset  with  actively  motile  flagella;  (5)  free  motile  flagella;  and  (6)  swollen 
spherical  or  deformed  bodies  8-10  [x.  in  diameter,  containing  pigment,  and 
regarded  as  cadaveric  forms  of  spherical  parasites.  Laveran  noted  amoeboid 
movements  of  the  spherical  forms,  grouping  of  the  small  spherical  bodies 
together  and  the  occurrence  of  small,  colorless,  motile  bodies,  without  specific 
characters,  which  he  suggested  may  perhaps  represent  the  first  phase  of 
development  of  the  parasitic  elements.  He  regarded  all  of  the  forms  as 
different  stages  of  development  of  the  same  species  of  organism,  and  con- 
sidered the  free  flagella,  which  he  believed  were  formed  within  the  spherical 
bodies  and  escaped  by  rupture  of  the  enveloping  membrane,  as  the  most 
characteristic  and  perfect  stage  of  development  of  the  parasite. 

'  Only  occasional  references  to  the  voluminous  literature  on  the  parasitology 
of  malaria  are  given  in  this  article.  A  full  table  of  references  to  the  works  treat- 
ing of  malarial  fever  since  the  recognition  of  its  parasitic  origin  up  to  and  partly 
including  the  year  1895  will  be  found  in  The  Malarial  Fevers  of  Baltimore,  by 
William  Sydney  Thayer,  M.  D.,  and  John  Hewetson,  M.  D.  (The  Johns  Hopkins 
Hospital  Reports,  V,  1895). 


468  MALARIA 

Laveran  communicated  his  results  to  his  colleague  Richard,  stationed  in 
Philippeville,  Algiers,  who  in  February,  1882,  published  a  communication 
confirming  Laveran's  observations  and  adding  certain  points  of  importance. 
He  describes  the  development  of  the  parasite  from  small,  perfectly  trans- 
parent bodies  contained  in  otherwise  normal  red  blood  corpuscles.  This 
clear  body  grows  larger,  forms  pigment  out  of  the  haemoglobin  of  the 
enveloping  red  corpuscle,  which  thereby  becomes  gradually  decolorized  and 
reduced  to  a  mere  colorless  shell-like  rim,  which  finally  ruptures  and  sets* 
free  the  parasite.  This  now  generally  accepted  view  as  to  the  intracorpuscu- 
lar  development  of  the  parasite,  which  was  first  announced  by  Richard,  was, 
however,  in  the  following  year  abandoned  by  him  in  favor  of  Laveran's 
view  that  the  parasites  develop  either  free  in  the  plasma  or  in  close  attach- 
ment to  the  surface  of  red  corpuscles  or  in  depressed  spots  on  the  surface. 
Richard  observed  amoeboid  movements  of  the  parasites,  and  noted  spherical 
bodies  with  a  central  block  of  black  pigment  from  which  delicate  lines 
radiated  so  as  to  produce  rosette  forms. 

Laveran  continued  to  publish  brief  communications  in  1882  and  1883, 
and  in  188-i  he  published  a  larger  work '  presenting  his  observations  and 
views  in  detail.  In  this  work  he  describes  more  fully  the  forms  already 
mentioned,  and  he  notes  the  occurrence  of  segmenting  forms,  which,  how- 
ever, he  interpreted  as  forms  of  degeneration,  not  of  reproduction. 

The  observations  of  Laveran  and  of  Richard  were  made  by  microscopical 
examination  of  the  fresh  blood.  In  1883  and  1884,  Marchiafava  and  Celli 
published  in  a  number  of  articles  the  results  of  their  studies  of  stained  speci- 
mens of  dried  malarial  blood.  With  the  exception  of  small,  spherical  stained 
bodies  in  the  red  blood  corpuscles,  which  they  thought  might  be  micrococci, 
they  interpreted  the  various  other  stained  and  usually  pigmented  bodies 
found  in  the  red  corpuscles  of  malarial  patients  as  probably  degenerative 
changes.  As  a  matter  of  fact,  the  coccus-like  dots  were  probably  in  part  Ehr- 
lich's  degenerations,  whereas  their  drawings  show  that  the  supposed  degen- 
erative forms  were  in  reality  the  actual  parasites,  which  in  many  of  their 
phases  were  accurately  depicted,  although  not  recognized  as  such. 

In  1885,  Councilman  and  Abbott  in  the  organs  from  two  cases  of  per- 
nicious comatose  fever  found  and  described  small  pigmented  hyaline  bodies 
in  and  outside  of  red  corpuscles,  most  abundantly  in  capillaries  of  the  brain. 

In  1885,  Marchiafava  and  Celli,  as  the  result  of  the  examination  of  fresh 
malarial  blood,  came  to  a  correct  interpretation  of  these  bodies  and  described 
them  fully  and  accurately.  They  emphasized  especially  the  amoeboid,  un- 
pigmented,  transparent  intracorpuscular  bodies,  to  which  they  gave  the 

•Laveran:    Traits  des  FIfevres  palustres,  Paris,  1884. 


MALARIA  469 

inaccurate  name  of  plasmodia,  which  has  been  widely  adopted.  They 
described  clearly  the  intracorpuscular  development  of  the  parasite,  the  for- 
mation of  pigment  out  of  the  blood  coloring  matter,  the  consequent  changes 
in  the  blood  corpuscles,  and  they  pointed  out  the  probable  reproductive 
nature  of  the  segmenting  bodies,  which  they  described  more  fully  and  accu- 
rately than  had  been  done  by  Laveran  and  Eichard.' 

The  publications  of  Marchiafava  and  Celli  attracted  wider  attention  than 
had  those  of  Laveran,  and  from  the  year  1885  up  to  the  present  time  there 
has  been  a  steady  flowing  stream  of  literature  upon  the  various  questions 
connected  with  the  parasitology  of  malaria. 

Immediately  following  the  confirmation  of  Laveran's  discoveries  by  Italian 
observers  came  similar  confirmation  from  Sternberg,  Councilman,  and 
Osier  (1886-87),  and  somewhat  later  by  James  (1888)  and  Dock  (1890),  in 
this  country,  and  within  a  few  years  numerous  reports  from  various  parts  of 
Europe,  America,  Asia,  and  Africa  demonstrated  the  invariable  association 
of  Laveran's  parasites  with  all  cases  of  malarial  fever.  There  are  no  observ- 
ers of  any  prominence  who,  with  sufficient  opportunity  and  training  for 
such  examinations,  have  failed  to  recognize  the  parasites  in  cases  of  malaria, 
uor  is  there  now  any  authoritative  voice  of  dissent  from  the  acceptance  of 
the  parasite  as  the  specific  cause  of  this  disease. 

Since  the  fundamental  researches  of  Laveran,  Eichard,  and  Marchiafava 
and  Celli  (1880-85)  other  observers  have  greatly  extended  our  knowledge  as 
to  many  details  concerning  the  structure  and  life  history  of  the  parasite  and 
its  relation  to  various  types,  phenomena,  and  lesions  of  malaria,  although 
not  a  few  important  questions  still  remain  unsettled.  The  most  important 
of  these  later  discoveries  are  due  to  the  demonstration  by  Golgi  (1885-86) 
of  a  definite  relation  between  the  cycle  of  development  of  the  parasite  and  the 
different  stages  of  malarial  fever,  and  to  the  recognition  by  Golgi  (1885-86) 
of  the  two  varieties  of  the  parasite  belonging  respectively  to  quartan  and  to 
tertian  fever,  and  by  Marchiafava  and  Celli  and  Canalis  (1889)  of  the 
variety  or  varieties  belonging  to  aestivo-autumnal  fever.  These  observations 
have  led  to  two  schools  of  doctrine — the  one,  headed  by  Laveran,  holding  to 
the  unity  of  a  pleomorphic  malarial  parasite,  the  other,  headed  by  Golgi  and 
other  Italian  writers,  upholding  the  plurality  of  malarial  parasites.  The 
latter  doctrine  has  the  larger  number  of  supporters. 

'  Marchiafava  and  Celli  claim  for  themselves  the  discovery  of  the  intracorpus- 
cular amoeboid  forms  with  and  without  pigment,  and  of  the  segmenting  forms, 
but  as  is  apparent  from  the  review  of  Laveran's  and  Richard's  preceding  publi- 
cations, this  claim  cannot  be  admitted.  Marchiafava  and  Celli,  however,  des- 
cribed and  interpreted  these  phases  of  the  parasite  far  better  than  Laveran,  and 
to  them  belongs  the  credit  of  demonstrating  the  intracorpuscular  development  of 
the  parasite. 


470  MALAEIA 

Dock  (1890-92)  was  the  first  to  differentiate  the  three  principal  varieties 
of  the  malarial  parasite  in  the  United  States,  and  recently  Thayer  and 
Hewetson  *  have  published  a  thorough  study  of  the  malarial  fevers  of  Balti- 
more with  careful  descriptions  of  these  varieties. 

Investigations  concerning  the  intimate  structure  of  the  malarial  parasites 
have  been  made  especially-  by  Celli  and  Guarnieri,  Grassi  and  Feletti,  Eoman- 
cwsky,  Sacharoff,  Mannaberg,  Antolisei,  Bastianelli  and  Bignami,  and  others. 

The  results  of  these  later  studies  concerning  the  malarial  parasites  will  be 
considered  in  various  parts  of  this  article.  They  are  fully  and  systematically 
presented  in  the  recent  monograph  of  Thayer  and  Hewetson,  already  cited. 

NOMENCLATURE 

Various  names  have  been  suggested  for  the  malarial  parasite.  Among 
these  may  be  mentioned  Oscillaria  malariae  (Laveran),  'Plasmodium 
malariae  (Marchiafavaand  Celli),  Haematomonas  malariae  (Osier),  Haema- 
tophyllum  malariae  (Metchnikoff),  Haemamoeha  malariae  (Grassi  and 
Feletti),  Haemococcidium  malariae  (L.  Pfeiffer),  Haemosporidium  mala- 
riae (Danilewsky),  Haematozoon  or  Haemoojtozodn  malariae  (Osier  and 
various  authors). 

Of  these  names,  Plasmodium  malariae  has  gained  wide  currency,  but  it  is 
on  zoological  grounds  singularly  inappropriate,  and  there  is  no  reason  why  it 
should  be  perpetuated. 

The  name  Haemosporidium  malariae  has  much  to  recommend  it,  but  it 
has  not  been  generally  adopted.  Upon  the  whole,  the  name  Haematozoon 
malariae,  which  expresses  nothing  as  to  the  zoological  classification  of  the 
parasite,  and  which  has  been  adopted  by  many  writers,  may  be  provisionally 
accepted  until  more  precise  knowledge  is  reached  concerning  the  zoological 
position  of  the  parasite.  Haemocytozoon  is  more  precise,  but  the  other  term 
has  the  advantage  of  greater  brevity. 

ZOOLOGICAL  POSITION  OF  THE  MALARIAL  PARASITE 

The  malarial  parasite  belongs  to  the  class  of  Protozoa,  under  which  name 
are  grouped  the  unicellular  organisms  with  the  physiological  characters  of 
animals.  Biitschli  divides  the  Protozoa  into  the  orders — Sarcodina,  Mas- 
tigophora,  Sporozoa,  and  Infusoria.  Grassi  and  Feletti  classify  the  malarial 
parasite  among  the  Sarcodina,  subdivision  Bhizopoda,  and  adopt  the  name 
Haemamoeha  malariae.  Antolisei  considers  that  the  parasite  belongs  to  the 
Gymnomyxa,  or,  more  precisely,  the  Proteomyxa  of  Eay  Lankester.  The 
great  majority  of  authors  classify  the  malarial  parasite  among  the  Sporo- 

'  Op.  cit. 


MALARIA  47i 

zoa,  which  are  divided  by  Balbiani  into  the  groups  Gregarinida,  Sarcospo- 
ridia,  Myxosporidia,  and  Microsporidia.  Under  the  Gregarinidae  are  in- 
cluded the  Coccidia,  with  which  some  writers  group  the  malarial  parasite. 
Kruse  makes  under  the  Gregarinidae  a  special  family  which  he  designates 
as  Haemogregarinidae,  and  to  which  he  refers  the  malarial  parasite  and 
similar  haemocytozoa  in  lower  animals.  Danilewsky  suggests  forming  a 
new  group  under  the  Sporozoa  to  be  called  Haemosporidia,  in  which  he  places 
the  malarial  and  similar  haematozoa,  and  Labbe  calls  the  group  Gymno- 
sporidia. 

As  we  know  nothing  of  the  malarial  parasite  in  the  outer  world,  it  is 
evident  that  our  knowledge  of  its  life  history  is  incomplete,  so  that  any 
attempt  at  zoological  classification  must  be  regarded  as  only  provisional. 
Such  information  as  we  possess  favors  classifying  the  parasite  among  the 
Sporozoa,  but  it  possesses  characters  which  do  not  enable  us  to  fit  it  exactly 
into  any  of  the  existing  subdivisions  of  the  Sporozoa,  so  that  the  suggestions 
of  Kruse  and  of  Danilewsky  of  establishing  a  new  subdivision  of  the  Sporo- 
zoa or  of  the  Gregarinidae  to  include  the  malarial  parasite  and  similar 
organisms  in  birds  seems  to  be  a  good  one,  and  the  name  Haemosporidia  for 
this  new  subdivision  appears  to  be  appropriate.  According  to  this  classifi- 
cation, the  malarial  parasite  may  be  called  Haemosporidium  malariae. 

METHODS  OF  INVESTIGATION 

The  methods  for  demonstrating  and  studying  the  malarial  parasite  will 
be  described  under  the  heading  "  Diagnosis."  It  may  here  be  stated  that 
generally  the  most  useful  procedure  is  the  examination  of  thin  layers  of 
fresh  blood  with  an  oil-immersion  objective.  The  description  of  the  parasite 
which  is  to  follow  is  based  mainly  upon  this  method.  This  procedure  may  be 
advantageously  combined  with  the  examination  of  stained  specimens.  For 
the  study  of  the  finer  details  of  structure  this  latter  method  is  indispensable. 

GENERAL   MORPHOLOGY  AND  BIOLOGY 

The  malarial  parasite  is  a  unicellular,  protozoan  organism  which  develops 
within  the  red  blood  corpuscles,  and  therefore  belongs  to  the  group  of 
Haemocytozoa.  As  will  be  described  subsequently,  organisms  closely  resem- 
bling the  malarial  parasite  have  been  found  in  the  blood  of  birds.  The 
numerous  attempts  to  cultivate  artificially  the  malarial  parasite  have 
hitherto  been  unsuccessful,  nor  has  this  organism  been  recognized  in  the 
outer  world.  Our  entire  knowledge  of  it  is  derived  from  its  study  in  human 
beings. 

Three  varieties  of  the  parasite  have  been  differentiated.  These  varieties 
are  that  of  quartan  fever,  that  of  tertian  fever,  and  that  of  aestivo-autumnal 


472  MALARIA 

fever.  This  last  variety  it  is  proposed  by  the  writer  to  call  Haematozoon 
malariae  falciparum.  Before  considering  the  justification  of  this  division 
and  the  special  characters  of  each  of  these  varieties  it  is  desirable  to  describe 
the  more  important  characters  common  to  all  varieties  of  the  malarial 
parasite. 

The  cycle  of  development  of  the  malarial  parasite  embraces  a  vegetative 
and  a  reproductive  phase.  Its  duration  varies  from  24:  to  72  hours,  accord- 
ing to  the  variety  of  parasite. 

The  vegetative  phase  begins  in  the  form  of  small,  colorless,  amoeboid, 
hyaline  bodies,  1-2  /x  in  diameter,  within  the  red  blood  corpuscles.'  These 
amoeboid  bodies  increase  in  size,  and,  with  the  occasional  exception  of  the 
aestivo-autumnal  variety,  they  develop  within  them  a  variable  number  of 
dark  pigment  granules,  situated,  as  a  rule,  near  the  margin  of  the  parasite. 
The  pigment  increases  in  amount  and  in  the  coarseness  of  the  granules  as 
the  organisms  continue  to  develop.  It  occurs  in  the  form  of  irregular  grains 
and  of  fine  rods,  which  may  be  in  active  motion  within  the  parasite. 

Having  attained  a  certain  stage  of  development,  which  differs  as  regards 
the  size  of  the  organism  in  the  different  varieties,  the  parasite  gradually 
ceases  its  amoeboid  movements,  assumes  a  spherical  or  oval  shape,  and  be- 
comes somewhat  sharper  in  contour.  In  this  condition  it  may  continue  for 
a  while  to  grow.  When  it  has  reached  its  full  size  it  may  completely  fill  the 
red  blood  corpuscle  or  may  occupy  only  a  small  part  of  it,  these  differences 
depending  mainly  upon  the  variety  of  parasite.  The  parasite  now  may  be 
called  the  full-grown  or  adult  form. 

"As  has  already  been  mentioned,  Laveran  believes  that  the  forms  of  the 
parasite  which  have,  since  the  publications  of  Marchiafava  and  Celli,  usually 
been  regarded  as  within  the  red  corpuscles,  are  attached  or  applied  (accoles)  to 
the  outer  surface  of  the  corpuscles.  Mannaberg  (1893)  has  again  raised  this  ques- 
tion by  his  statement  that  many  of  the  amoeboid  forms,  particularly  in  their 
younger  stages  of  development,  are  attached  to  the  corpuscles,  often  in  little 
niches  or  indentations  on  the  surface.  There  is  no  doubt  that  the  organism  may 
be  situated  as  described  by  Mannaberg.  Marchiafava  and  Celli,  who  had  previ- 
ously noted  this  appearance,  interpreted  it  as  indicating  the  extrusion  of  the 
parasite  from  the  red  blood  corpuscle.  It  is,  in  fact,  often  very  difficult  to  deter- 
mine with  precision  whether  the  organism  is  on  the  surface  of  or  within  the 
corpuscle,  but  the  evidence  is  that  the  majority  of  the  younger  forms  are  intra- 
corpuscular.  Marchiafava  and  Bignami  (1894)  describe  in  the  following  words 
their  conception  of  the  manner  of  penetration  of  the  youngest  forms  into  the 
corpuscle:  "The  youngest  amoebae,  the  offspring  of  sporulation,  by  virtue  of 
the  viscidity  of  their  protoplasm  adhere  to  the  surface  of,  and  by  their  move- 
ments bury  themselves  in,  the  contour  of  the  red  corpuscle.  In  this  position  the 
parasite  attacks  the  external  strata  of  the  corpuscle  as  a  means  of  nourishment, 
and  after  altering  these  layers  is  able  to  penetrate  within,  and  thus  becomes 
entirely  endoglobular." 


MALAEIA  473 

Coincidently  with  these  stages  of  development  the  enveloping  red  blood 
corpuscle  may  undergo  various  changes,  which  are  of  significance  in  dis- 
tinguishing the  varieties  of  parasite  from  each  other.  The  corpuscle  may  be- 
come swollen  and  pale,  or  shrunken,  or  brassy  green  in  color,  or  otherwise 
deformed,  or  it  may  appear  unaltered,  as  will  be  described  in  considering 
the  varieties  of  the  parasite. 

The  subsequent  stages  in  this  cycle  of  development  belong  to  the  reproduc- 
tive phase,  which  is  shorter  in  duration  than  the  vegetative.  The  first  evi- 
dence of  this  reproductive  phase  is  the  collection  of  the  pigment  into  a  mass 
of  granules  or  a  solid  block  situated  usually  at  or  near  the  centre,  but  some- 
times near  the  periphery,  of  the  organism.  These  bodies  with  clumps  of 
pigment  may  be  designated,  in  accordance  with  Thayer  and  Hewetson's  sug- 
gestion, as  the  presegmenting  forms  {corpi  con  blocchetto  of  the  Italian 
writers). 

Coincidently  with  or  following  this  gathering  of  the  pigment  into  a  clump, 
sometimes  without  a  definite  collection  of  the  pigment,  the  process  of  seg- 
mentation begins.  In  its  most  typical  form  segmentation  is  ushered  in  by 
the  appearance  of  delicate  lines  radiating  from  the  periphery  toward  the 
centre.  Eventually  the  substance  of  the  spherical  organism  is  divided  into  a 
variable  number  of  round  or  oval  bodies  called  spores.  The  enveloping  red 
corpuscle,  which  now  may  be  reduced  to  a  narrow  pale  rim,  bursts  and  the 
spores  are  set  free,  or  the  corpuscle  may  have  disappeared  before  the  process 
of  segmentation  is  completed.  The  pigment  remains  behind,  and  is  quickly 
engulfed  by  phagocytes.  Sometimes  in  the  aestivo-autumnal  variety  seg- 
mentation occurs  in  organisms  entirely  devoid  of  pigment.  These  segment- 
ing bodies  are  called  also  sporulating  forms. 

The  free  spores  speedily  invade  fresh  red  Iplood  corpuscles,  where,  as  the 
small,  colorless,  amoeboid,  hyaline  bodies  already  mentioned,  they  begin 
again  the  cycle  of  development.  The  direct  transformation  of  the  motion- 
less ^°  round  spores  into  the  small,  hyaline,  amoeboid  bodies  has  been  very 
rarely  observed,  but  there  is  no  reason  to  suppose  that  there  exists  any  stage 
intervening  between  these  two  forms. 

In  the  complete  sporulating  cycle  of  development  which  has  been  described 
we  can  distinguish,  therefore,  the  following  forms  of  the  parasite :  ( 1 )  un- 
pigmented,  amoeboid,  hyaline  bodies;  (2)  pigmented,  amoeboid,  hyaline 
bodies;  (3)  full-grown  or  adult  bodies ;  (4)  presegmenting  bodies ;  (5)  seg- 
menting or  sporulating  bodies;  and  (6)  spores. 

^°  Plehn  claims  to  have  observed  that  the  spores  are  actively  motile  and  flagel- 
lated, but  this  statement  is  opposed  to  the  observations  of  all  others. 

33 


474  MALARIA 

As  already  mentioned,  in  the  aestivo-autumnal  variety  this  cycle  may  be 
completed  without  the  appearance  of  pigment.  These  bodies  are  to  be 
thought  of,  not  as  separate  and  distinct  forms,  but  simply  as  successive  stages 
of  development  with  all  transitions  from  the  youngest  to  the  most  advanced. 
Especially  can  no  sharp  distinction  be  drawn  between  bodies  (1)  and  (2) 
and  between  bodies  (3)  and  (4).  The  recognition,  as  a  distinct  form,  of  the 
body  designated  as  presegmenting  is  of  less  practical  importance  for  the 
quartan  and  tertian  varieties  than  for  the  aestivo-autumnal. 

The  name  "  plasmodium  "  was  applied  by  Marchiafava  and  Celli  originally 
to  the  unpigmented,  amoeboid  forms.  It  is  frequently  employed  to  designate 
both  the  pigmented  and  the  unpigmented  amoeboid  bodies,  as  well  as  the 
parasite  in  all  of  its  forms.  These  amoeboid  bodies  may  be  called,  in  general, 
hyaline  forms  or  amoebae. 

As  will  be  explained  subsequently,  it  is  only  the  quartan  variety  which  is 
found  in  all  its  forms  with  equal  frequency  in  the  peripheral  circulation 
and  in  the  blood  of  internal  organs;  whereas  segmenting  tertian  parasites 
are  more  abundant  in  the  spleen  and  bone  marrow  than  in  the  peripheral 
vessels,  and  the  aestivo-autumnal  parasite  develops  mainly  in  the  internal 
organs,  its  segmenting  forms  being  extremely  rare  in  the  peripheral  circu- 
lation. 

Each  of  the  forms  of  the  parasite  which  have  been  described  as  developing 
within  the  red  blood  corpuscles  may  also  be  found  free  in  the  plasma.  They 
probably  escape  by  rupture  of  the  enveloping  corpuscle,  a  process  which  one 
can  often  witness  when  examining  the  fresh  blood  microscopically.  Extra- 
corpuscular  mature  forms  may  possibly  segment  in  the  usual  way,  but  there 
is  no  evidence  that  forms  in  the  earlier  stages  may  complete  their  cycle  of 
development  free  in  the  plasma. 

The  important  discovery  was  made  by  Golgi  that  all  of  one  generation  of 
the  parasite  form  a  group,  the  members  of  which  develop  approximately  at 
the  same  time,  and  that  a  definite  relation  exists  between  the  phases  of  de- 
velopment of  the  parasite  and  the  stages  of  malarial  fever.  The  onset  of  a 
paroxysm  corresponds  to  the  ripening  of  one  generation  of  the  parasite.  A 
few  hours  or  shortly  before  the  paroxysm  segmenting  forms  appear,  and 
enable  the  observer  to  predict  the  approaching  paroxysm.  The  spores  which 
are  set  free  by  the  act  of  sporulation  invade  the  red  blood  corpuscles  and 
start  a  fresh  generation,  which  pursues  during  the  paroxysm  and  the  subse- 
quent apyrexia  so  regular  a  development  that  in  typical  cases  the  experienced 
observer  can  tell  approximately  by  examination  of  the  blood  the  stage  of  the 
disease — that  is,  the  time  which  has  elapsed  since  the  last  paroxysm  and  the 
time  when  the  next  paroxysm  may  be  expected. 


MALAEIA  475 

It  is  not,  however,  always  the  case  that  the  parasite  develops  with  the 
regularity  expressed  by  Golgi's  law,  and  especially  in  the  aestivo-autumnaJ 
fevers  irregularities  are  very  common.  The  simultaneous  occurrence  of  two 
or  more  generations  in  different  stages  of  development  may  render  difficult 
the  interpretation  of  the  phases  observed,  although  even  liere  careful  observa- 
tion will  enable  the  observer  to  draw  correct  conclusions  in  tertian  and  quar- 
tan fevers. 

It  has  not  been  satisfactorily  demonstrated  that  there  occurs  any  other 
cycle  of  development  of  the  malarial  parasite  in  human  beings  than  that 
which  has  been  described,  although  the  possibility  of  such  an  occurrence  is 
by  no  means  disproven.  Canalis  (1889)  believes  that  he  has  found  evidence 
that  a  second,  slower  cycle  of  development  of  the  aestivo-autumnal  parasite 
occurs,  which  is  represented  in  certain  of  its  phases  by  bodies  of  the  crescentic 
group,  to  be  described  subsequently;  and  this  view,  with  certain  modifica- 
tions, has  been  accepted  by  Golgi,  Antolisei  and  Angelini,  Grassi  and  Feletti, 
and  Sacharoff.  This  doctrine  is,  however,  opposed  by  many  observers,  and 
it  does  not  at  present  rest  upon  sufficient  evidence. 

It  seems  necessary  to  suppose,  on  the  basis  of  clinical  evidence,  that  the 
malarial  parasite  may  remain  for  months  in  a  latent  condition  in  the  human 
body,  and  then  begin  to  develop  again,  causing  a  relapse  of  the  fever.  As 
such  relapses  may  occur  in  forms  of  malaria  in  which  crescents  do  not  appear, 
there  must  be  in  these  cases  some  resistant  organism  other  than  bodies  be- 
longing to  the  group  of  crescents.  We  know  nothing  as  to  the  nature  of 
these  resistant  bodies.  The  hypothesis  is  advanced  by  Bignami  that  they 
may  be  spores  which  are  enclosed  within  leucocytes  and  other  cells,  and  which 
have  become  surrounded  by  a  resistant  membrane  and  have  lost  their  usual 
staining  properties. 

Besides  the  forms  which  have  already  been  described  as  representing 
phases  of  the  regular  sporulating  cycle  of  development  of  the  malarial  para- 
site, there  occur  other  forms  which  cannot  at  present  be  referred  to  any  cycle 
of  development.  These  other  forms  are — (1)  crescentic  bodies  and  fusi- 
form, oval,  and  round  bodies  belonging  to  the  same  group;  (2)  flagellate 
bodies  and  free  flagella;  and  (3)  degenerative  forms. 

The  crescentic  and  flagellate  bodies,  from  their  size  and  remarkable  appear- 
ance, are  the  most  striking  forms  of  the  parasite,  and  from  the  beginning 
have  attracted  much  attention.  Their  significance,  although  there  are  many 
hypotheses  concerning  it,  is  not  understood. 

(1)  The  crescents  develop  only  from  the  aestivo-autumnal  parasites,  and 
will  therefore  be  described  in  connection  with  these.  They  are  never  formed 
from  quartan  and  tertian  parasites. 


476  MALARIA 

(2)  Flagellate  bodies,  on  the  other  hand,  may  form  from  each  variety 
of  the  parasite,  tertian,  quartan,  or  aestivo-autumnal.  The  weight  of  evi- 
dence is  that  they  do  not  exist  in  the  circulating  blood,  but  develop  after  the 
blood  has  been  withdrawn  from  the  body,  usually  within  ten  to  twenty 
minutes,  sometimes  earlier.  Some  observers  have  found  them  frequently, 
others  only  rarely.  They  are  frequently  found  if  the  blood  is  examined  at 
the  right  stage  of  the  disease  and  time  is  allowed  for  their  development. 
Councilman  showed  that  they  are  more  commonly  found  in  blood  aspirated 
by  a  hypodermic  needle  from  the  spleen  than  in  the  peripheral  blood.  They 
develop  in  tertian  and  quartan  fevers  from  the  mature,  full-grown  extracor- 
puscular  forms — in  tertian  especially  from  swollen  forms  larger  than  the  red 
blood  corpuscles.  They  are  therefore  found  most  frequently  a  short  while 
before  and  during  the  paroxysm.  In  infections  with  the  aestivo-autumnal 
parasite  the  flagellate  bodies  develop  from  round  bodies  belonging  to  the 
group  of  crescents,  and  do  not  occur  in  definite  relation  to  the  stage  of  the 
fever.    Earely  intracorpuscular  bodies  may  develop  flagella. 

The  spherical  bodies  which  become  transformed  into  the  flagellate  bodies 
are  always  or  nearly  always  pigmented.  Marchiafava  and  Celli  state  that 
they, once  saw  an  unpigmented  flagellate  body.  These  bodies  may  be  some- 
what smaller  or  larger  than  the  red  blood  corpuscles,  the  size  varying  to  some 
extent  with  the  different  varieties  of  the  parasite,  as  will  be  explained  later. 
The  process  of  development  of  the  flagella  may  be  studied  under  the  micro-, 
scope.  The  pigment  granules,  which  at  first  (aestivo-autumnal  variety) 
may  have  been  in  repose,  usually  begin  to  dance  about  within  the  organism, 
often  in  a  lively  way.  In  the  aestivo-autumnal  variety  they  usually  gather  in 
the  central  part,  but  in  the  others  they  may  be  near  the  periphery  or  irregu- 
larly distributed.  The  spherical  body  may  acquire  an  oscillatory  or  jerking 
movement.  Projections  may  be  formed  and  retracted  at  the  periphery,  and 
the  whole  edge  may  acquire  a  vigorous  undulating  movement.  These  changes 
are  attributed  to  the  movements  of  the  flagella  within  the  body  or  in  its 
peripheral  layers,  and  have  been  graphically  compared  by  Richard  to  the 
struggles  of  an  animal  to  get  free.  Suddenly  the  flagella  shoot  out  from  the 
periphery,  and  with  their  active  lashing  movements  produce  a  violent  com- 
motion among  the  red  blood  corpuscles  and  other  small  particles  which  may 
be  in  their  neighborhood. 

The  flagella  are  pale  and  thin,  and  present  often  at  their  extremities  and 
along  their  course  small  olive  shaped  swellings  which  may  change  their 
position.  Here  and  there  a  pigment  granule  is  occasionally  seen  in  a  flagel- 
lum.  The  flagella  vary  in  size,  number,  and  position.  Their  length  may  be 
three  or  four  times  the  diameter  of  a  red  blood  corpuscle  or  not  more  than 
half  that  size.  One  to  six  may  be  attached  to  the  spherical  body.  They  may 
project  from  one  side  or  from  any  part  of  the  circumference  of  the  body. 


MALARIA  477 

Their  movements  may  be  somewhat  rhythmical;  they  may  become  slow  or 
even  cease,  and  again  start  up. 

Flagella  may  become  detached  and  move  about  freely  among  the  red  blood 
corpuscles.  On  account  of  their  pallor  such  free  flagella  would  usually  be 
overlooked  were  it  not  for  the  commotion  which  they  produce  among  the  red 
blood  corpuscles.  The  motion  of  the  flagella  may  be  observed  on  the  slide 
for  half  an  hour,  sometimes  longer. 

These  flagellate  bodies  are  the  most  startling  forms  of  the  malarial  organ- 
ism, and  no  one  who  sees  them  doubts  for  a  moment  that  he  is  looking  at  a 
living  parasite.  It  is  not  surprising  that  they  attracted  in  an  especial  man- 
ner the  attention  of  Laveran,  who,  as  already  mentioned,  regarded  the  flagella 
as  the  most  characteristic  and  perfect  form  of  development  of  the  parasite. 
Subsequent  studies  have  not,  however,  tended  to  confirm  the  conception  of 
Laveran  as  to  their  significance.  As  has  already  been  made  clear,  the  flagel- 
lated bodies  do  not  belong  to  the  regular  sporulating  cycle  of  development 
of  the  malarial  parasite  in  the  human  blood.  The  most  prominent  theories 
as  to  their  significance  are  the  following: 

(a)  They  are  forms  of  degeneration  or  appearances  .belonging  to  the  death 
agony  of  the  parasite.  In  support  of  this  view  it  is  urged  that  the  flagellate 
bodies  do  not  belong  to  any  known  cycle  of  development;  that  they  are  de- 
veloped only  outside  of  the  human  body;  that  they  are  developed  from 
mature  forms  which  are  known  frequently  to  undergo  undoubted  degenera- 
tion, such  as  hydropic  swelling,  vacuolation,  and  fragmentation,  and  which 
may  already  show  beginning  evidences  of  degeneration;  that  nuclear  sub- 
stance is  absent  from  the  flagella ;  and  that  similar  appearances  of  extrusion 
of  motile  filaments  in  other  unicellular  organisms  are  known  to  zoologists 
and  are  interpreted  as  degenerative. 

(6)  Sacharoff,  from  the  study  of  their  structure  on  stained  specimens, 
believes  that  the  flagella  are  extruded  chromatin  filaments  derived  from 
perverted  karyokinetic  nuclear  division.  He  regards  the  process  as  degen- 
erative. 

(c)  Dock  suggests  that  the  flagellate  bodies  "represent  resting  states  of 
the  organism,  capable  of  existing  independently,  perhaps  even  of  reproduc- 
ing themselves,  but  also  able,  under  favorable  circumstances,  of  reproducing 
the  typical  growth  of  the  parasite." 

(d)  Mannaberg's  opinion  is  that  the  flagellate  bodies  may  represent  a 
state  belonging  to  the  saprophytic  existence  upon  which  the  mature  forms 
of  the  parasite  enter  soon  after  the  blood  is  withdrawn  from  the  body.  On 
account  of  unsuitable  conditions  of  environment  they  are  unable  to  continue 
this  existence  in  the  blood  outside  of  the  body  and  soon  perish.  A  similar 
view  is  advanced  by  Manson,  who  suggests  that  the  flagellate  bodies  repre- 


478  MALAEIA 

sent  the  first  stage,  and  the  detached  flagella,  in  search  of  their  appropriate 
host,  represent  the  second  stage  of  life  of  the  parasite  outside  of  the  body. 
Manson  "  conjectures  that  the  mosquito  is  the  extracorporeal  host  of  the 
malarial  parasite,  and  he  reports  observations  of  Ross  showing  the  develop- 
ment of  flagellate  forms  in  the  stomach  of  mosquitoes  fed  on  malarial  blood. 

There  are  arguments  for  and  against  each  of  these  theories.  Eeluctant  as 
one  may  be  to  consider  such  striking  forms  as  the  flagellate  bodies  as  phases 
of  degeneration,  the  existing  evidence  seems  upon  the  whole  to  be  more  in 
favor  of  this  hypothesis  than  of  any  other  which  has  been  advanced.  Still, 
if  Sacharoff^s  obsen^ation  as  to  tbe  presence  of  nuclear  material  in  the  flagella 
be  correct,  the  objection  of  Grassi  and  Feletti,  that  the  flagella  are  incapable 
of  reproductive  development  because  the  nucleus  of  the  parasite  does  not 
divide  and  enter  them,  would  be  overthrown  and  the  hypothesis  of  Manna- 
berg  and  Manson  would  become  more  probable.  It  is  evident  from  the  de- 
scription of  these  bodies  that  the  use  of  the  word  "  flagella  "  to  designate  the 
motile  filaments  is  of  doubtful  propriety,  but  it  is  the  term  commonly 
employed. 

(3)  There  are  various  bodies,  often  seen  in  the  examination  of  malarial 
blood,  which  are  undoubtedly  degenerative  forms  of  the  parasite,  and  others 
which  are  probably  degenerative,  although  opinions  concerning  the  latter 
are  divided.  The  more  common  signs  of  degeneration  of  the  parasite  are 
vacuolation,  pseudo-gemmation,  fragmentation,  deformities  of  shape,  par- 
ticularly swelling,  granular  condition  of  the  protoplasm,  certain  alterations 
in  the  arrangement  and  appearance  of  the  pigment,  disappearance  of  nuclear 
material,  defects  and  irregularities  in  staining,  and  changes  in  the  refraction 
of  the  organism.  These  various  degenerative  changes  produce  forms  too 
numerous  to  describe  in  detail.  They  have  often  been  misinterpreted  and 
described  as  special  forms  of  the  parasite,  some  of  them,  particularly  certain 
vacuolated  and  budding  forms,  as  special  modes  of  reproduction. 

Degenerations  may  occur  in  any  form  of  the  parasite,  but  they  are  par- 
ticularly common  in  the  extracorpuseular  forms.  Mannaberg  describes  the 
disintegration  of  young  intracorpuscular  forms,  with  disappearance  of  their 
nuclei.  Fragmentation  of  forms  extruded  from  the  blood  corpuscles  can 
sometimes  be  watched  while  examining  fresh  blood  under  the  microscope. 
As  a  rule,  only  a  ccrt^iin  number  of  the  mature  forms  actually  enter  into  re- 
productive segmentation,  and  many  of  the  spores  or  segments  perish.  If  all 
segmented  and  the  offspring  survived,  the  number  of  the  parasites  after  a 

"  Manson:  The  Goulstonian  Lectures  on  the  Life  History  of  the  Malaria  Germ 
Outside  the  Human  Body  (The  British  Medical  Journal,  1896,  March  14,  21,  28). 
Manson  lays  much  emphasis  upon  supposed  analogies  between  the  malarial  germ 
and  Filiaria  sangtiinis.  Only  future  investigations  can  determine  the  correct- 
ness of  Manson's  hypothesis. 


MALARIA  479 

few  paroxysms  would  become  enormous.  As  a  matter  of  fact,  degenerations 
of  full-grown  parasites  are  often  observed.  An  interesting  form  of  such 
degeneration,  found  most  frequently  in  the  mature  forms  of  the  tertian 
variety,  is  the  appearance  of  swollen,  pigmented,  so-called  hydropic  bodies, 
often  much  larger  than  red  blood  corpuscles,  and  sometimes  containing 
vacuoles.  Eound  bodies  simulating  spores  are  sometimes  seen  in  these 
vacuoles,  but  on  properly  stained  specimens  they  are  devoid  of  the  nuclear 
material  of  genuine  spores.  Pseudo-gemmation,  or  the  appearance  of 
sarcodic  buds  on  the  surface  of  the  organisms,  is  doubtless  a  form  of  degenera- 
tion. Such  buds  may  become  separated,  in  the  form  of  hyaline  balls,  from 
the  parent  organism.  These  evidences  of  degeneration  may  appear  also  in 
crescents  and  bodies  belonging  to  this  group  and  in  flagellate  bodies.  From 
the  latter  small  hyaline  balls  with  a  flagellum  attached  may  break  off  and 
move  around  actively.    Such  bodies  might  be  mistaken  for  flagellated  spores. 

There  is  no  good  evidence  that  the  malarial  parasite  ever  multiplies  by 
budding  "  or  by  simple  cell  division.  The  only  form  of  multiplication  which 
has  been  demonstrated  is  that  of  sporulation,  also  called  segmentation, 
already  described,  although  it  cannot  be  denied  that  other  forms  of  repro- 
duction may  exist. 

Various  interesting  degenerative  changes  are  produced  by  the  influencu 
of  quinine.  These  will  be  fully  described  under  Treatment,  Action  of 
Quinine  on  Malarial  Parasites  (page  146,  Vol.  I,  Syst.  Pract.  M.  [Loomis] 
1897). 

As  the  malarial  parasite  passes  its  vegetative  life  mostly  within  the  red 
blood  corpuscles,  it  is  evident  that  it  finds  its  food  in  this  situation.  This 
food  may  be  appropriated  both  by  intussusception  and  by  diffusion.  Evi- 
dence of  intussusception  is  found  in  the  occasional  presence  of  fragments 
of  the  corpuscular  substance  within  the  body  of  the  amoeboid  forms.  Doubt- 
less diffusion  is  the  more  important  mode  of  nutrition  of  the  parasite. 

The  question  has  been  raised  whether  the  parasite  may  develop  in  other 
cells  of  the  body  than  the  red  blood  corpuscles.  Nearly  all  forms  of  the 
parasite  have  been  found  enclosed  in  cells,  chiefly  leucocytes,  splenic  or 
medullary  cells,  and  endothelial  cells.  As  such  included  parasites  often 
present  evidences  of  degeneration,  these  appearances  have  been  generally 
interpreted  as  referable  to  phagocytic  destruction  of  the  parasites,  and  such 
they  unquestionably  usually  are.     Golgi  and  Monti  have,  however,  recently 

"  Celli  and  Guarnieri  for  a  time  believed  that  spherical  bodies  of  the  crescentic 
phase  may  multiply  by  the  formation  of  buds  (gemmation),  but  they  subse- 
quently abandoned  this  view  and  adopted  the  now  generally  accepted  opinion 
that  these  budding  forms  are  degenerative.  The  "  buds  "  are  now  devoid  of  the 
structure  of  genuine  spores. 


480  MALARIA 

published  observations  intended  to  show  that  the  aestivo-autumnal  parasite 
may  develop  within  endothelial  and  other  cells,  as  will  be  explained  in  con- 
sidering this  variety  of  parasite. 

The  malarial  parasite  in  the  condition  in  which  it  exists  in  the  human 
body  is  very  susceptible  to  injurious  agencies.  It  is  quickly  killed  by  the 
addition  of  distilled  water  and  of  dilute  acids  and  alkalies.  Under  ordinary 
conditions  it  does  not  long  survive  in  blood  withdrawn  from  the  body.  Under 
certain  special  circumstances  it  has  been  kept  apparently  alive  from  two  to 
four  days,  possibly  for  a  week.  Sacharoff  observed  amoeboid  movements  in 
aestivo-autumnal  hyaline  bodies  which  had  been  for  a  week  in  the  intestinal 
canal  of  leeches  kept  on  ice,  and  he  obtained  a  positive  result  by  inoculating 
himself  with  malarial  blood  preserved  in  this  way  for  four  days  in  leeches. 
The  tertian  and  quartan  parasites  were  found  to  be  less  resistant  than  the 
aestivo-autumnal.  Ripe  bodies  may  segment  in  blood  outside  of  the  body, 
but  no  further  development  or  multiplication  of  the  parasites  has  been  posi- 
tively observed  in  the  various  attempts  made  to  preserve  or  cultivate  them. 
The  parasite  does  not  continue  to  develop  and  multiply  in  the  human  body 
after  death. 

Of  course  no  inferences  can  be  drawn  from  these  observations  as  to  the 
resistance  of  the  parasite  in  its  natural  condition  in  the  outer  world.  As  to 
what  this  natural  condition  is  we  can  only  speculate.  Grassi  and  Caland- 
niccio  have  thought  that  certain  species  of  amoebae  which  they  have  ob- 
served in  malarial  districts  might  be  the  extraparasitic  form.  The  failure 
of  artificial  cultivations  and  certain  analogies  drawn  from  the  zoological 
characters  of  the  parasite  have  led  to  the  prevalent  theory  that  the  malarial 
parasite  passes  at  least  a  part  of  its  existence  as  a  parasite  in  animal  or 
vegetable  organisms.  Mention  has  already  been  made  of  Manson's  hypothe- 
sis that  the  mosquito  may  be  a  host  for  the  malarial  parasite.  That  the 
germ  is  capable  of  entering  upon  some  resistant  phase  of  development  seems 
highly  probable  in  view  of  the  evidence  that  malaria  can  be  contracted  from 
the  air.  There  is  no  evidence  that  the  malarial  parasite  is  eliminated  from 
the  human  body  in  a  condition  capable  of  infecting  another  individual  or 
the  locality.  The  disease,  however,  can  be  transmitted  by  inoculating 
into  healthy  individuals,  either  subcutaneously  or  intravenously,  blood  from 
a  malarial  patient. 

UNITY    OR    PLURALITY   OF    THE    MALARIAL   PARASITE 

As  has  already  been  mentioned,  there  are  two  schools  of  doctrine  as  to 
the  malarial  parasite — the  one  led  by  Laveran  holding  that  the  malarial 
parasite  is  a  single  species  with  pleomorphic  characters,  the  other  believing 
that  there  are  three  or  more  species,  or  at  least  varieties,  of  malarial  parasites. 


MALARIA  481 

The  observations  upon  which  the  latter  doctrine  is  based  originated  with  the 
Italians,  and  have  been  supported  by  investigations  in  this  country  and 
elsewhere. 

Golgi  in  1885  and  1886  first  differentiated  the  parasite  of  quartan  fever 
from  that  of  tertian  fever,  and  Marchiafava  and  Celli  and  Canalis  in  1889 
and  1890  differentiated  the  variety  of  parasite  characteristic  of  aestivo- 
autumnal  fever."  There  is  much  difference  of  opinion  as  to  the  number  of 
aestivo-autumnal  parasites.  All  adherents  of  the  doctrine  of  plurality  agree 
that  there  are  at  least  three  varieties  of  malarial  parasite — namely,  the 
quartan,  the  tertian,  and  the  aestivo-autumnal — distinguished  from  each 
other  by  morphological  and  biological  characters  to  be  subsequently  de- 
scribed. The  discovery  by  Golgi  of  the  definite  cycle  of  development  of  the 
malarial  parasite  and  the  recognition  of  several  distinct  varieties  have  done 
much  to  bring  order  out  of  the  earlier  chaotic  condition  when  a  multitude 
of  parasitic  bodies  were  described  without  knowledge  of  their  significance 
or  relations  to  each  other.  There  remain,  however,  many  unsolved  problems 
which  it  may  be  expected  that  further  investigations  will  clear  up. 

In  opposition  to  the  doctrine  of  plurality  it  is  urged  by  Laveran  that  all  of 
the  so-called  varieties  of  the  parasite  may  be  explained  simply  as  phases  of 
a  single  pleomorphic  organism  influenced  by  various  conditions  of  environ- 
ment, such  as  locality,  season,  individual  predisposition,  and  various  un- 
known circumstances.     He  contends  that  the  characters  upon  which   a 

^  Marchiafava  and  Celli  on  the  one  hand,  and  Canalis  on  the  other  hand,  have 
conducted  a  polemic  as  to  which  of  them  belongs  the  credit  of  first  distinguishing 
the  aestivo-autumnal  parasite.  The  differentiation  of  this  parasite  was  not  made 
all  at  once,  and  with  the  same  precision  in  all  details,  as  in  the  case  of  Golgi's 
sharp  separation  of  the  quartan  and  tertian  parasites.  Golgi  from  the  beginning 
of  his  researches  (1885-86)  suggested  that  the  crescentic  bodies  belong  to  a 
special  cycle  of  existence  different  from  that  of  the  tertian  and  quartan  organ- 
isms, and  noted  their  occurrence  in  irregular  malarial  fevers.  Councilman  in 
1887  emphasized  the  association  of  crescents  with  remittent  fevers  and  malarial 
cachexia.  Golgi  in  February,  1889,  definitely  expressed  the  opinion  that  in 
addition  to  the  malarial  fevers  caused  by  the  quartan  and  the  tertian  parasites 
we  must  recognize  another  type  of  fever  associated  with  unpigmented  amoeboid 
forms  and  crescents.  On  September  13,  1889,  appeared  a  preliminary  commu- 
nication of  Marchiafava  and  Celli,  which  must  be  regarded  as  furnishing  the 
first  clear  and  sharp  description  of  the  essential  differential  characters  of  the 
aestivo-autumnal  parasite,  with  especial  emphasis  on  the  occurrence  of  unpig- 
mented organisms.  On  October  10,  1889,  appeared  the  preliminary  communica- 
tion of  Canalis,  in  which  likewise  the  essential  Characters  of  this  parasite  were 
discribed,  and  greater  emphasis  was  laid  upon  its  relation  to  the  crescents  than 
had  been  done  by  Marchiafava  and  Celli.  The  full  publication  of  Canalis  antici- 
pated by  a  short  time  the  complete  article  of  Marchiafava  and  Celli  on  the 
aestivo-autumnal  parasite. 


483  MALAEIA 

division  into  separate  varieties  is  based  are  insufficient  for  such  a  purpose 
and  inconstant;  that  one  so-called  variety  under  certain  conditions  may  be 
transformed  into  another;  and  that  there  is  no  definite,  necessary  relation 
between  the  types  of  fever,  such  as  quartan,  tertian,  quotidian,  irregular, 
continued,  and  the  form  of  parasite  present.  The  variations  of  the  malarial 
parasite  can  be  explained,  he  thinks,  in  large  part  by  the  varying  rapidity 
of  development.  He  emphasises  the  view  that  malaria  with  all  its  diverse 
manifestations  is  nevertheless  clinically  and  anatomically  one  disease,  and 
has  always  been  so  regarded.  He  argues  that  the  experimental  production 
of  malaria  by  inoculation  does  not  support  the  doctrine  of  plurality. 

In  considering  the  force  of  these  objections  it  must  be  admitted  that  so 
long  as  we  are  unable  to  cultivate  the  malarial  parasite  artificially,  and  are 
ignorant  of  its  life  history  and  the  conditions  of  existence  outside  of  the 
himian  body,  the  possibility  must  be  admitted  that  under  certain  conditions, 
at  present  unknown,  one  variety  may  be  transformed  into  another.  But,  on 
the  other  hand,  the  existing  evidence — and  it  is  already  considerable — goes 
to  show  that  under  the  conditions  which  we  can  at  present  control  and  study 
each  of  the  three  principal  varieties  of  the  parasite  preserves  its  identity 
and  is  not  transformed  into  another  variety ;  that  is  to  say,  there  is  no  evi- 
dence that  a  quartan  parasite  ever  becomes  metamorphosed  into  a  tertian, 
or  either  of  these  into  an  aestivo-autumnal  parasite. 

The  principal  arguments  in  support  of  this  doctrine  of  plurality  may  be 
summarized  as  follows: 

(1)  Each  well-established  variety  of  parasite  presents  morphological  and 
biological  characters  which  suffice  for  its  identification. 

(2)  Each  variety  of  parasite  corresponds  to  definite  types  of  fever. 
Genuine  quartan  fever  can  be  produced  only  by  the  quartan  parasite.  As 
will  be  explained  in  the  clinical  part  of  this  article,  other  types  of  fever  may 
be  caused  by  more  than  one  variety  of  parasite,  and  much  complexity  may  re- 
sult from  multiple  and  mixed  infections  and  various  irregularities ;  but  all 
of  this  does  not  prevent  the  recognition  of  certain  fimdamental  types  of 
fever  especially  characteristic  of  each  variety  of  the  parasite. 

(3)  Cases  of  pure  infection  with  one  variety  of  parasite  have  been  care- 
fully studied  for  weeks  and  months  without  any  indication  of  the  transfor- 
mation of  one  variety  into  another  ( Calandruccio,  Grassi  and  Feletti). 
Opportunities  for  such  study  are  exceptional.  The  appearance  of  a  second 
variety  of  parasite  in  localities  where  there  is  opportunity  for  renewed  in- 
fection cannot  of  course  be  interpreted  in  favor  of  the  metamorphosis  of  one 
variety  into  another. 

(4)  In  certain  localities  only  one  or  two  of  the  varieties  of  the  parasite 
are  met  with.    In  a  few  places  only  the  quartan,  or  more  frequently  only  the 


MALAEIA  483 

tertian,  parasite  is  observed;  in  most  places  where  malaria  is  mild  and  in- 
frequent only  tertian,  and  occasionally  quartan,  parasites,  with  entire  absence 
of  aestivo-autumnal  parasites,  are  found.  Instances  of  this  localized  dis- 
tribution of  the  parasites,  which  manifestly  is  a  strong  argument  in  favor 
of  the  doctrine  of  plurality,  will  be  subsequently  mentioned  (page  99,  Vol. 
I,  "Syst.  Pract.  M."  [Loomis],  1897). 

(5)  Strong  arguments  in  favor  of  the  constancy  of  the  varieties  of  the 
malarial  parasite  are  furnished  by  the  experimental  production  of  malaria. 
Gerhardt  in  1882  and  1883  (reported  in  1884)  was  the  first  to  produce 
malaria  experimentally  by  the  subcutaneous  injection  of  blood  obtained 
from  malarial  patients.  At  this  time  the  malarial  organism  was  not  generally 
recognized.  Since  these  first  experiments  similar  ones  have  been  repeated, 
usually  in  the  manner  of  intravenous  injections  of  malarial  blood,  with 
positive  result  in  over  thirty  cases.  The  experiments  before  1889  were  made 
without  determination  of  the  exact  variety  of  parasite  injected  and  found 
in  the  experimental  case.  In  1889,  Gualdi  and  Antolisei,  without  full  knowl- 
edge of  the  critical  nature  of  the  experiment,  injected  two  patients  intra- 
venously with  3  c.  c.  of  blood  from  a  patient  suffering  with  quartan  fever 
and  possessing  quartan  parasites.  In  each  of  the  inoculated  individuals 
irregular  fever  with  aestivo-autumnal  parasites  developed.  These  two  cases 
are  constantly  adduced  as  a  main  support  of  the  doctrine  of  mutability  of 
the  varieties  of  the  parasite,  but  unjustly  so,  for  it  was  subsequently  de- 
termined that  the  patient  from  whom  the  blood  was  obtained  had  previously 
suffered  from  irregular  fever,  and  he  subsequently  developed  characteristic 
aestivo-autumnal  organisms,  so  that  the  experimenters  themselves  later 
expressed  the  opinion  that  at  the  time  of  the  inoculation  the  patient  furnish- 
ing the  blood  had  combined  quartan  and  aestivo-autumnal  organisms,  the 
latter  being  overlooked.  In  view  of  the  uniform  results  yielded  by  the 
numerous  subsequent  experiments  in  support  of  the  doctrine  of  immuta- 
bility of  the  varieties  of  the  parasite  there  can  be  little  doubt  that  this  later 
opinion  of  Gualdi  and  Antolisei  is  correct.  It  has  been  found  regularly 
since  these  experiments  that  if  blood  containing  only  the  tertian  or  the 
quartan  or  the  aestivo-autumnal  parasite  be  injected  intravenously  into  a 
person  unaffected  with  malaria,  the  variety  of  parasite  injected,  and  only 
that  variety,  appears  in  the  blood  of  the  experimental  case.  When  two 
varieties  of  parasite  are  injected,  or  when  the  malarial  blood  is  injected  into 
a  patient  already  affected  with  a  malarial  organism  other  than  that  injected, 
then  it  usually  happens  that  one  variety  supplants  the  other,  most  frequently 
the  one  injected  supplanting  that  already  existing  in  the  inoculated  indi- 
vidual. For  such  displacement  of  one  organism  by  another  we  have  nu- 
merous examples  in  bacterial  infections. 


484  MALARIA 

The  bearing  of  the  inoculation  experiments  upon  the  determination  of 
the  periods  of  incubation  of  malaria  will  be  considered  in  the  clinical  part 
of  this  article  (pages  97,  98,  Vol.  I,  "  Syst.  Pract.  M."  [Loomis],  1897). 

These  already  numerous  inoculation  experiments,  showing  the  identity 
of  the  parasite  in  the  experimental  case  with  that  in  the  blood  used  for  in- 
jection, furnish  the  strongest  existing  arguments  in  favor  of  the  plurality 
of  the  malarial  parasites." 

Whether  accepting  this  doctrine,  we  shall  designate  the  different  typea 
of  the  malarial  organism  as  separate  species  or  separate  varieties  is  with 
our  present  knowledge  a  matter  of  secondary  importance  and  of  individual 
judgment.  If  it  be  admitted  that  under  no  existing  circumstances  one  type 
is  transformed  into  another,  then  we  are  justified  in  speaking  of  separate 
species  of  malarial  parasites.  As  at  present  we  can  study  only  a  small 
part  of  the  conditions  which  surround  the  entire  life-history  of  the  parasite, 
it  seems  to  the  writer  preferable  to  designate  the  different  types  as  varieties 
rather  than  species. 

CLASSIFICATION 

We  have  already  had  occasion  repeatedly  to  mention  the  division  of  the 
malarial  parasites  into  three  principal  varieties — the  quartan,  the  tertian, 
and  the  aestivo-autumnal.  No  further  subdivisions  of  the  quartan  variety 
has  ever  been  suggested.  Nor  has  any  attempt  been  made  to  subdivide  the 
tertian  parasite  originally  described  by  Golgi ;  but,  as  it  has  since  been  found 
that  the  aestivo-autumnal  parasite — or,  according  to  some  observers,  one 
form  of  this  parasite — may  likewise  produce  tertian  fever,  the  latter  form 
of  the  aestivo-autumnal  organism  is  designated  by  Marchiafava  and  Bignami 
as  malignant  tertian  or  aestivo-autumnal  (summer-autumn)  tertian,  and 
the  former  called  mild  or  vernal  (spring)  or  genuine  tertian  or  Golgi's 
tertian  parasite.  This  so-called  aestivo-autumnal  or  malignant  tertian  is, 
however,  in  no  sense  a  subdivision  of  the  tertian  parasite  originally  de- 
scribed by  Golgi,  which  remains  a  well-differentiated,  separate  variety. 
When  the  name  "  tertian  organism  "  is  used  without  any  epithet,  it  is  always 
this  variety  which  is  meant. 

The  name  "  parasite  of  aestivo-autumnal  fever,"  introduced  by  March- 
iafava and  Celli  and  already  adopted  by  many  writers,  leaves  much  to 
be  desired.  It  is  intended  to  indicate  that  this  form  of  the  parasite  is  the 
cause  of  the  malarial  fevers  prevailing  in  summer  and  autumn.  This  appli- 
cation, however,  is  correct  only  for  certain  localities,  chiefly  those  warmer 
regions  where  severe  as  well  as  mild  types  of  malaria  occur.     In  localities 

"  Di  Mattel:  Contribute,  alio  Studio  della  Infezione  Malarica  Sperimentale 
neir  Uomo  e  negli  Animali.  Arch,  per  le  Scienze  Mediche,  XIX,  N.  4,  1895. 


MALARIA  485 

where  the  prevailing  type  of  the  disease  is  mild  at  all  seasons  the  summer 
and  autumn  malarial  fevers  are  caused  generally  or  exclusively  by  tertian 
or  quartan  parasites.  Even  in  the  warmer  situations  where  the  aestivo- 
autumnal  parasite  is  common,  not  all  of  the  summer-autumn  fevers  are 
caused  by  this  parasite,  but  often  a  large  proportion  are  caused  by  the  ordi- 
nary tertian  parasites.  In  subtropical  and  tropical  regions  the  aestivo- 
autumnal  parasites  may  occur  in  winter  and  spring  fevers.  It  is  evident 
that  the  epithet  "  aestivo-autumnal,"  as  applied  to  a  special  variety  of  ma- 
larial parasite,  is  sufficiently  designative  for  many  localities,  as,  for  example, 
the  southern  parts  of  the  United  States  and  Central  and  Southern  Italy, 
but  it  is  not  so  for  all. 

The  term  "  parasite  of  aestivo-autumnal  fever  "  does  not  at  once  suggest 
the  relation  of  the  parasite  to  a  definite  type  of  malarial  fever,  and  is  there- 
fore out  of  harmony  with  the  designations  "  parasite  of  quartan  fever  "  and 
"  parasite  of  tertian  fever."  But  it  is  characteristic  of  a  large  proportion  of 
the  fevers  caused  by  aestivo-autumnal  organisms  that  they  do  not  correspond 
to  any  definite  type,  but  are  notably  irregular.  Hence  these  organisms  were 
designated  by  Golgi  and  by  SacharoS  as  the  "  parasite  of  irregular  malarial 
fevers."  But  the  objection  to  this  latter  name  is  that  aestivo-autumnal 
organisms  may  cause  typical  quotidian  and  tertian  fevers.  Indeed,  this  is 
the  only  form  of  malarial  parasite  which,  it  is  believed,  may  complete  its 
cycle  of  development  in  twenty-four  hours,  and  thus  when  present  in  only  a 
single  group  or  generation  may  cause  quotidian  fever. 

As  leading  characters  of  the  aestivo-autumnal  organisms  are  their  small 
size,  their  slight  formation  of  pigment,  and  the  ring-like  shape  of  the 
amoeboid  forms,  they  are  sometimes  spoken  of  as  the  small  malarial  organ- 
isms {forme  piccole).,  or  the  unpigmented,  colorless,  or  slightly  pigmented 
organisms,  or  the  ring-like  annular  organisms.  They  are  also  called  the 
organisms  of  grave  or  pernicious  malaria,  although  they  may  likewise  cause 
mild  types  of  the  disease. 

As  it  is  to  the  group  of  aestivo-autumnal  parasites  that  the  crescents  ex- 
'elusively  belong,  these  parasites  have  been  described  as  the  semi-lunar 
variety.  They  may  be  designated  as  crescent-producing.  Haematozoon 
falciparum  is  suggested  by  the  writer  as  a  suitable  technical  name  for  this 
variety  of  parasite.'" 

^'  The  name  Haematozoon  falciforme  suggested  by  Antolisei  and  Angelini  is 
objectionable,  as  it  implies  that  the  shape  is  always  falciform,  and  is  applicable 
only  to  the  crescentic  forms.  The  adjective  "  falciparum "  Ualx,  "  sickle," 
parire,  "to  bring  forth,"  "to  produce"),  on  the  other  hand,  indicates  that  the 
property  of  forming  crescents  is  a  distinctive  character  of  the  organism,  and  it 
is  therefore  applicable  to  the  variety  of  the  parasite  which  possesses  exclusively 
this  property. 


486  MALAEIA 

The  three  varieties  of  the  malarial  parasite  may  therefore  be  technically 
designated — (1)  Haematozoon  fehris  quartanae;  (2)  Haematozoon  fehris 
tertanae;  (3)  Haematozoon  malariae  falciparum.  The  name  aestivo- 
autumnal  parasite,  as  the  more  commonly  used  and  generally  understood 
designation,  will,  however,  continue  to  be  used,  as  well  as  the  term  "  Haema- 
tozoon falciparum,"  in  this  article  for  the  last  named  variety. 

There  is  no  difference  of  opinion,  except  among  the  unicists,  that  the 
aestivo-autumnal  organisms  form  a  variety  or  group  which  is  to  be  differen- 
tiated from  both  the  quartan  and  the  tertian  organisms  even  more  sharply 
than  the  tertian  and  the  quartan  are  differentiated  from  each  other.  But 
the  question  as  to  the  unity  or  the  plurality  of  the  aestivo-autumnal  organ- 
isms is  still  an  open  one,  and  is  the  most  important  unsolved  problem  re- 
lating to  the  divisions  of  malarial  parasites.  Its  solution  is  attended  with 
unusual  difficulties,  but  we  may  reasonably  expect  that  they  will  be  sur- 
mounted by  future  investigations. 

In  distinction  from  the  quartan  and  the  tertian  organisms  the  aestivo- 
autumnal  are  often  irregular  and  atypical  in  their  cycle  of  development. 
Some,  it  is  believed,  may  complete  their  cycle  in  twenty-four  hours,  others  in 
forty-eight  or  a  longer  period :  their  tendency  to  develop  simultaneously  in 
well  defined  generations  is  far  less  marked  than  is  the  case  with  tertian  and 
quartan  organisms,  so  that  several  or  all  phases  of  development  of  aestivo- 
autumnal  forms  may  be  observed  in  the  internal  organs  at  the  same  time. 
The  occurrence  of  multiple  groups  of  the  parasite  is  common.  Forms 
appear  which  pass  through  their  amoeboid,  mature,  and  segmenting  phases 
without  any  formation  of  pigment  within  the  parasite.  The  development 
takes  place  largely  in  the  internal  organs.  The  development  of  crescents 
occurs  at  a  variable  period  after  the  onset  of  the  disease,  but  rarely  in  less 
than  a  week.  Corresponding  to  these  variations  and  irregularities  the  types 
of  fever  with  which  aestivo-autumnal  organisms  are  associated  are  various 
and  irregular. 

The  attempt  has  been  made  to  deduce  certain  laws  controlling  these 
variations  and  apparent  irregularities,  and  to  subdivide  the  aestivo- 
autumnal  organisms  into  certain  varieties  or  subvarieties,  but  there  is  little 
agreement  of  opinion  as  to  this  subdivision. 

The  following  are  the  principal  divisions  of  the  malarial  parasite  which 
have  been  proposed,  the  essential  differences  in  these  various  divisions  re- 
lating, of  course,  to  the  different  views  held  concerning  the  aestivo-autumnal 
organisms : 

I.  Marchiafava  and  Colli  (1889)  recognized  a  short  cj^cle  of  development 
of  the  aestivo-autumnal  parasite,  unaccompanied  by  development  of  pig- 
ment, and  a  longer  cycle  with  formation  of  a  few  pigment  granules.    Mar- 


MALAEIA  487 

chiafava  and  Bignami  (1891)  make  two  varieties  of  this  parasite — viz. 
the  amoeba  of  aestivo-autumnal  quotidian,  with  twenty-four-hour  cycle, 
and  the  amoeba  of  aestivo-autumnal  tertian,  with  a  forty-eight-hour  cycle — 
Amoeba  fehris  quotidianae  and  Amoeba  febris  tertinae  aestivo-autumnalis. 
The  latter  variety  is  the  malignant  tertian  organism  of  these  authors.  The 
main  differences  between  these  varieties,  according  to  IMarchiafava  and  Big- 
nami, relate  to  the  length  of  the  cycle  of  development,  but  there  are  claimed 
to  be  also  minor  morphological  and  biological  differences  to  be  mentioned 
subsequently  (pp.  503  and  504). 

These  authors,  therefore,  make  four  different  varieties  of  the  malarial 
parasite.    They  divide  the  malarial  fevers  into  two  main  groups : 

1.  Mild  malarial  fevers  which  prevail  in  winter  and  spring.    These  are — 
(a)   Quartan  fever  (with  its  varieties  of  double  and  triple  quartan) .    This 

caused  by  the  Amoeba  febris  quartanae  (Golgi),  which  completes  its  life 
cycle  in  seventy-two  hours. 

(6)  Tertian  fever  (with  double  tertian  and  rarely  certain  suhcontinued 
fevers).  This  is  caused  by  the  Amoeba  febris  tertianae  (Golgi),  which 
completes  its  life  cycle  in  forty-eight  hours. 

2.  Severe  or  aestivo-autumnal  fevers,  including  the  pernicious  and  most 
of  the  suhcontinued  fevers.    This  group  comprises — 

(a)  Aestivo-autumnal  quotidian  fever  (to  be  distinguished  from  quo- 
tidians of  tertian  and  of  quartan  origin),  caused  by  the  Amoeba  febris  quo- 
tidianae, which  completes  its  cycle  in  twenty-four  hours.  This  is  the  only 
variety  of  malarial  parasite  which  can  complete  its  life  cycle  in  so  short  a 
period  as  twenty-four  hours. 

(&)  Aestivo-autumnal  or  malignant  tertian  fever,  caused  by  the  Amoeba 
febris  tertianae  aestivo-autumnalis,  which  completes  its  cycle  in  forty-eight 
hours.  Most  of  the  pernicious  cases  belong  to  this  variety,  the  remainder 
to  the  aestivo-autumnal  quotidian  variety. 

II.  Canalis  (1889)  does  not  subdivide  into  varieties  the  aestivo-autumnal 
parasite,  which  he  calls  the  "  semilunar  variety,"  but  he  considers  that  it  has 
two  cycles  of  development:  (a)  a  rapid  cycle  with  the  usual  phases  of 
amoeboid,  mature,  segmenting  forms  and  spores,  and  (b)  a  slower  cycle 
associated  with  the  development  of  crescentic  bodies,  which  he  considers  to 
be  reproductive  and  to  represent  one  phase  in  this  second  cycle.  A  similar 
view  is  held  by  Antolisei  and  Angelini. 

III.  Grassi  and  Feletti  (1890)  regard  the  crescent-producing  forms  as 
an  entirely  separate  species,  which  they  call  Laverania  malariae,  and  which 
they  distinguish  both  from  the  directly  spore-forming  unpigmented  aestivo- 
autumnal  forms,  which  they  call  Haemamoeba  immaculata  and  from  similar 


488  MALARIA 

rapidly  developing,  but  pigmented,  aestivo-autunmal  parasites,  without 
crescents,  which  they  call  Haemamoeha  praecox.  Their  classification  of 
the  malarial  parasite  is  as  follows :  (a)  Haemamoeha  malariae,  identical  with 
the  quartan  parasite;  (b) Haemamoeha  vivax,  which  is  identical  with  the 
tertian  parasite  of  Golgi;  (c)  Haemamoeha  praecox,  a  form  of  the  aestivo 
autumnal  parasite,  giving  rise  to  quotidian  fever;  {d)  Haemamoeha  imma- 
culata,  similar  to  the  preceding,  but  without  development  of  pigment;  (e) 
Laverania  malariae,  the  crescent-producing  variety,  giving  rise  to  irregular 
fevers. 

S'acharoff  formerly  regarded  the  crescents  as  belonging  to  a  separate  species 
of  malarial  parasite,  and  adopted  the  following  classification :  (a)  Haema- 
moeha fehris  quartanae  (Golgi),  (&)  Haemamoeha  fehris  tertianae  (Golgi), 
(c)  Haemamoeha  praecox  (Grassi),  {d)  Laverania  (Grassi).  Kecently 
(1896)  he  holds  that  all  variations  of  the  aestivo-autumnal  parasite  are 
modifications  of  a  single  variety  due,  mainly,  to  the  development  of  the 
parasite  within  nucleated  red  blood  corpuscles. 

IV.  Mannaberg  (1893)  accepts  Marchiafava  and  Bignami's  division  of 
aestivo-autumnal  parasites  into  quotidian  and  tertian,  and  also  adopts  Grassi 
and  Feletti's  division  into  pigmented  and  unpigmented  quotidian  parasites. 
He  does  not,  however,  consider  the  crescents  as  belonging  to  a  species  or 
variety  distinct  from  these,  but  considers  them  as  developing  from  each  of 
these  three  divisions  of  aestivo-autumnal  parasites.  He  has  a  peculiar  view 
as  to  the  origin  of  the  crescents  from  conjugation  of  cells,  and  regards  them, 
therefore,  as  forms  of  syzygia.  He  divides  the  malarial  parasites  into  two 
groups — the  first  group,  with  sporulation  and  without  syzygia,  comprising 
(a)  the  quartan  and  (6)  the  tertian  parasites  of  Golgi;  the  second  group, 
with  sporulation  and  with  syzygia,  comprising  {a)  the  pigmented  quotidian 
parasite,  (6)  the  unpigmented  quotidian  parasite,  and  (c)  the  malignant 
tertian  parasite. 

V.  Golgi  (1893),  an  admirable  and  successful  investigator  of  the  malarial 
parasites,  does  not  consider  the  semilunar  forms  as  belonging  to  a  species  or 
variety  distinct  from  the  ordinary  sporulating  aestivo-autumnal  parasite. 
He  attempts  no  subdivision  of  the  aestivo-autumnal  parasite.  His  concep- 
tion of  the  mode  of  development  of  this  parasite  differs  in  essential  points 
from  that  of  Marchiafava  and  Bignami  and  of  most  other  investigators,  as 
will  be  explained  in  considering  the  special  characters  of  the  aestivo- 
autumnal  parasite. 

The  following  statement  of  Golgi's  classification  of  the  malarial  fevers  is 
quoted  from  Thayer  and  Hewetson's  work  on  "  The  Malarial  Fevers  of 


MALAEIA  489 

Baltimore/'  already  cited."  Golgi  divides  the  malarial  fevers  into  two 
groups : 

(1)  Fevers  the  pathogensis  of  which  is  connected  with  parasites  which 
have  their  principal  habitat  in  the  circulating  blood  where,  by  preference, 
they  accomplish  the  phases  of  their  cycle  of  existence. 

(2)  Fevers  the  pathogenesis  of  which  is  connected  with  parasites  which 
have  their  chief  seats  in  the  internal  organs,  particularly  the  bone  marrow 
and  the  spleen,  where,  by  preference,  they  accomplish  their  cycle  of  existence 
in  conditions  of  relative  stability. 

(1)  The  fevers  of  the  first  group  are  unquestionably  associated  with  dif- 
ferent species  or  varieties  of  the  parasite — viz.  (a)  the  quartan  parasite; 
(&)  the  tertian  parasite. 

(2)  "To  the  second  group  belong  the  fevers  which  appear  clinically 
under  multiform  types,  very  often  irregular,  of  which  for  the  present  it  is 
impossible  to  make  a  grouping  based  upon  an  ascertained  biology  or  cycle 

of  development  of  the  parasite We  are  dealing  in  these  cases  vsdth 

generations  of  parasites  which,  occurring  in  the  parenchyma  of  organs  in 
different  stages  of  development,  give  origin,  at  periods  of  a  certain  regularity 
or  in  a  more  or  less  continuous  succession,  to  colonies  of  young  forms  which, 
in  large  or  small  numbers  or  in  insignificant  quantity,  may  escape  into  the 
blood  current,  permitting  one  to  discover  by  microscopical  examination  of 
the  blood  the  presence  of  the  small  endoglobular  amoebae."  Golgi  refers  to 
the  crescents  as  "  forms  the  biology  of  which  has  not  yet  been  well  deter- 
mined." 

VI.  Thayer  and  Heweston  (1895)  were  likewise  unable  to  confirm  Mar- 
chiafava  and  Bignami's  subdivision  of  the  aestivo-autumnal  parasite  into  a 
quotidian  and  a  tertian  variety.  They  say :  "  We  have  been  unable  to  trace 
a  constant  length  of  the  cycle  of  development,  and  we  have  been  unable  fur- 
ther to  separate  two  or  more  types  of  the  [aestivo-autumnal]  parasite  de- 
pending either  upon  the  length  of  the  cycle  of  development  or  upon  any 
other  morphological  or  biological  differences.  We  believe  that  the  length  of 
the  cycle  varies  greatly  in  different  cases,  lasting  usually  from  twenty-four 
hours,  or  even  a  little  less,  to  forty-eight  hours  or  more.  After  the  infection 
is  five  days  or  a  week  old  certain  of  the  organisms,  instead  of  segmenting, 
pursue  a  further  growth,  developing  into  the  hyaline,  refractive,  ovoid,  and 
crescentic  bodies."  They  do  not  feel  justified  in  making  any  positive  state- 
ment as  to  the  significance  or  capacity  of  reproductive  development  of  the 
crescentic  bodies. 

"  The  writer  wishes  to  acknowledge  his  indebtedness  to  this  excellent  mono- 
graph for  much  valuable  assistance  in  the  preparation  of  this  article. 

34 


490  MALAEIA 

The  question  has  been  raised  whether  in  tropical  regions,  where  pernicious 
types  of  malaria  are  common,  any  form  of  malarial  parasite  different  from 
those  already  mentioned  occurs.  The  observations  of  Vandyke  Carter, 
Dock,  van  der  Scheer,  Plehn,  and  others  show  that  the  same  parasites  are 
found  in  India,  Panama,  Java,  and  other  tropical  countries  as  elsewhere. 
The  negative  reports  which  have  been  published  are  referable  doubtless  to 
insufficient  training  in  such  examinations  on  the  part  of  the  observers.  The 
fact  that  a  large  part  of  tlie  tropical  malarial  fevers  are  caused  by  aestivo- 
autumnal  organisms  which  appear  in  the  red  blood  corpuscles  as  small,  pale, 
feebly  staining,  delicate,  diaphanous,  often  unpigmented  amoeboid  rings  of 
hyaline  protoplasm,  difficult  to  detect  in  many  cases,  and  sometimes  scanty 
or  at  times  even  absent,  will  account  for  many  of  these  negative  observations. 

The  singular  distribution  of  the  haemoglobinuric  type  of  pernicious 
malarial  fevers  in  certain  definite  localities  suggests  the  possibility  that  this 
may  be  caused  by  a  special  type  of  organism.  The  sporadic  cases  of  malarial 
haemoglobinuria  examined  in  Italy  have  shoAvn,  however,  ordinary  aestivo- 
autumnal  organisms.  Plehn  "  found  in  cases  of  black-water  fever  occurring 
on  the  West  Coast  of  Africa  small,  annular  amoeboid  forms,  staining  with 
great  difficulty  and  never  pigmented,  in  the  red  blood  corpuscles.  "  Out  of 
the  amoeba  there  develops  by  thickening  of  the  peripheral  zone  an  oval  or 
egg-shaped  body,  with  well  staining  double  contour.  In  course  of  time  this 
divides  into  five  or  six  small  oval  forms,  staining  at  one  pole,  which,  when 
they  are  set  free,  move  about  with  great  rapidity  in  the  blood.  These  prob- 
ably develop  into  the  amoeboid  forms."  The  organism  never  attained  a  size 
larger  than  one-quarter  of  the  red  blood  corpuscle.  Crescents  were  occa- 
sionally found.  Plehn  seems  to  regard  this  organism  as  allied  to,  but  not 
identical  with,  the  aestivo-autumnal  parasite  described  by  Italian  writers. 
Although  his  description  presents  certain  peculiarities  of  the  parasite  which 
he  observed  in  the  pernicious  malarial  haemoglobinuria  and  other  pernicious 
fevers  of  the  West  Coast  of  Africa,  especially  the  constant  absence  of  pig- 
ment, the  extremely  small  size,  the  sporulation  in  the  blood,  and  the  appar- 
ently motile  spores,'*  nevertheless  it  is  not  sufficiently  complete  and  satis- 
factory to  justify  the  inference  that  the  organism  differs  from  forms  of 
the  ordinary  aestivo-autumnal  parasite  as  previously  observed. 

From  the  preceding  review  of  the  various  investigations  and  opinions 
concerning  the  divisions  of  varieties  of  the  malarial  parasite,  especially  of  the 

"Plehn:  Ueber  das  Schwarzwasserfieber  an  der  afrikanischen  Westkiiste, 
Deutsche  med.  Wochenschrift,  1895,  Nos.  25,  26,  27. 

""  It  may  here  be  mentioned  that  Plehn  considers  that  the  spores  of  all  varieties 
of  the  malarial  parasite  are  flagellated — a  view  which  has  not  been  confirmed  by 
other  observers. 


MALARIA  491 

aestivo-autumnal  form,  we  may  draw  the  conclusion  that  whereas  the  separa- 
tion into  quartan,  tertian,  and  aestivo-autumnal  varieties  rests  upon  a 
sound  basis  of  fact,  the  various  attempts  to  further  subdivide  the  aestivo- 
autumnal  group  have  not  as  yet  been  sufficiently  successful  to  justify  our 
acceptance  at  the  present  time  of  any  of  these  subdivisions.  There  is,  how- 
ever, some  reason  to  believe  that  this  last  group,  as  at  present  constituted, 
may  comprise  varieties  which  will  hereafter  be  satisfactorily  differentiated 
from  each  other. 

We  will  now  consider  the  special  characters  of  each  of  the  three  varieties 
of  the  malarial  parasite. 

I.  THE  PARASITE  OF  QUARTAN  FEVER  (HAEMATOZOON  FEBRIS  QUARTANAE) 

In  most  malarial  regions  this  is  the  rarest  form  of  the  malarial  parasite, 
but  there  are  certain  places  (none  of  these  have  been  recognized  in  this 
country)  where  it  is  the  prevailing  variety.  Being  particularly  common  in 
the  neighborhood  of  Pavia  in  Italy,  the  quartan  parasite  was  the  first  to  be 
differentiated  and  described  by  Golgi  (1885-86),  to  whose  masterly  descrip- 
tion nothing  of  essential  importance  has  been  added  by  subsequent  investi- 
gators, with  the  exception  of  certain  details  of  intimate  structure. 

The  quartan  parasite  completes  its  cycle  of  development  in  seventy-two 
hours  and  entirely  within  the  circulating  blood.  The  youngest  forms  of 
the  parasite  are  small,  amoeboid,  when  at  rest  discordial,  hyaline  bodies, 
within  the  red  blood  corpuscles.  They  are  about  one-fifth  to  one-fourth 
the  size  of  the  red  blood  corpuscles.  The  central  part  of  the  body  may 
appear  paler  than  the  peripheral.  These  unpigmented,  youngest  forms  are 
found  during  and  for  several  hours  after  the  paroxysm ;  they  may  begin  to 
appear  two  hours  before  the  paroxysm.  The  very  earliest  forms  are  not  to  be 
distinguished  from  the  youngest  tertian  parasites,  but  as  they  begin  to 
develop  they  present  a  sharper  outhne  and  somewhat  more  refractive  appear- 
ance, and  their  amoeboid  movements  are  more  sluggish  and  restricted  than 
those  of  the  corresponding  stages  of  the  tertian  organism.  These  movements 
become  more  active  on  the  warm  stage  of  the  microscope.  The  presence  of 
more  than  one  parasite  in  a  red  blood  corpuscle  is  sometimes  observed. 

Shortly,  or  within  twelve  to  eighteen  hours,  after  the  paroxysm  pigment 
granules  appear  within  these  hyaline  bodies,  which  continue  to  increase 
slowly  in  size,  and  for  a  while  to  exhibit  lazy  amoeboid  movements.  The 
pigment  appears  in  the  form  of  brownish  or  black  rods  and  grains,  which 
are  coarser  and  darker  than  those  seen  in  tertian  parasites.  The  rod  form  of 
pigment  is  less  common  than  in  the  tertian  organism.  These  pigment 
granules  are  arranged  generally  in  the  peripheral  part  of  the  parasite,  and 
they  present  only  a  sluggish  movement  in  comparison  with  the  active  motion 


493  MALAEIA 

of  the  pigment  in  the  tertian  parasite.  With  the  gradual  increase  in  size 
of  the  hyaline  bodies  and  in  the  amount  of  contained  pigment  the  red  blood- 
corpuscles  enclosing  them  may  appear  unchanged,  or  often  they  become  a 
little  smaller,  more  refractive,  and  deeper  in  color,  which  may  be  somewhat 
greenish  or  coppery  in  tint.  There  is  not  that  tendency  to  decolorization  and 
swelling  of  the  infected  red  blood  corpuscles  which  is  noticed  in  the  case  of 
the  tertian  parasite,  although  in  the  more  advanced  stages  of  development 
there  is  usually  some  loss  of  color  in  red  corpuscles  containing  quartan 
organisms. 

In  the  process  of  development  the  amoeboid  movements  cease,  and  the 
parasite  appears  as  a  quiescent,  pigmented,  spherical,  or  ovoid  body  occupy- 
ing perhaps  one-half  to  two-thirds  of  the  red  corpuscles.  Such  bodies  are 
usually  seen  within  forty-eight  hours  after  the  paroxysm.  These  bodies 
continue  to  grow,  and  when  they  have  reached  their  full  development  in 
sixty  to  seventy  hours  after  the  paroxysm  they  are  somewhat  smaller  than  the 
normal  red  blood  corpuscles.  These  full-grown  forms  are  spherical  or  ovoid, 
refractive,  hyaline  bodies,  with  nearly  or  quite  motionless  dark  pigment 
granules  of  variable  size,  but  coarser  than  in  the  tertian  parasite,  and  with 
a  tendency  to  peripheral  arrangement,  but  at  times  irregularly  distributed. 
Around  these  bodies  a  thin  layer  of  the  colored,  refractive  substance  of  the 
red  blood  corpuscle  can  usually  still  be  seen,  or  the  haemoglobin  may  be  en- 
tirely removed,  so  that  only  a  delicate,  thin,  colorless  rim  or  line  surrounding 
the  parasite  is  all  that  is  left  of  the  original  red  blood  corpuscle.  In  unstained 
specimens  these  latter  forms  often  appear  to  be  free  in  the  plasma,  and  are 
sometimes  spoken  of  as  free  bodies,  which  may  also  occur. 

In  six  or  eight  to  ten  hours  before  the  febrile  paroxysm  the  first  phases  of 
reproduction  begin  to  appear.  These  are  ushered  in  by  the  gradual  with- 
drawal of  the  pigment  from  the  periphery  toward  the  centre  of  the  body. 
The  pigment  in  this  process  is  often  arranged  in  definite  radial  striae.  Such 
regular  stellate  arrangements  of  the  pigment  as  are  seen  in  this  stage  of  the 
quartan  parasite  are  rarely,  if  ever,  observed  in  the  tertian  (Thayer  and 
Hewetson).  Finally  the  pigment  is  concentrated  into  a  central  mass  of 
granules  or  a  solid  block  of  coalesced  pigment,  less  frequently  into  two  or 
more  collections,  and  the  organisms  assume  a  somewhat  more  refractive 
and  slightly  granular  appearance. 

At  the  same  time  or  soon  afterward  radial  divisional  striae  begin  to  appear 
in  the  periphery,  and  quickly  extend  to  the  central  part  of  the  parasite, 
whereby  the  substance  of  the  spherical  organism  becomes  divided  into  six  to 
twelve  ovoid  or  pear-shaped  segments  arranged  with  characteristic  and  ex- 
quisite regularity  around  the  central  mass  of  pigment  like  the  petals  of  a 
daisy  (rosettes  of  Golgi).    In  each  of  the  segments  can  be  seen  a  small  round 


MALAKIA  493 

glistening  body  which  represents  the  nucleus  or  nuclear  material.  The 
pyriform  segments  assume  rapidly  a  round  or  oval  shape,  and  become 
separated  from  the  central  mass  and  from  each  other.  The  delicate  envelop- 
ing membrane,  which  may  not  be  recognized  on  unstained  specimens,  de- 
rived from  the  red  blood  corpuscle  ruptures,  or  it  may  previously  have  disap- 
peared, and  the  small  round  or  oval  bodies,  each  provided  with  a  bright 
nucleiform  dot,  are  set  free  in  the  plasma.  These  bodies  are  the  so-called 
spores.  Simultaneously  with  this  process  of  sporulation  young  amoeboid 
hyaline  bodies,  formed  directly  from  the  spores,  make  their  appearance  in 
the  red  blood  corpuscles,  and  the  cycle  of  development  is  completed  and 
another  cycle  is  begun. 

Segmenting  or  sporulating  forms  of  the  parasite  may  appear  six  or  eight 
hours  before  the  paroxysm,  and  are  most  abundant  shortly  before  and  during 
the  onset  of  the  paroxysm.  It  is  of  course  not  to  be  understood  that  all  of 
the  parasites  of  one  group  pass  through  their  developmental  phases  and 
mature  at  exactly  the  same  moment.  One  parasite  of  the  group  may  be 
several  hours  in  advance  of  another,  but  this  does  not  interfere  with  the 
recognition  of  distinct  groups  or  generations,  each  standing  in  definite  rela- 
tion to  a  paroxysm,  or  with  the  establishment  of  Golgi's  law  that  the  onset 
of  each  paroxysm  corresponds  to  the  maturation  of  one  group  of  organisms. 

The  cycle  of  development  of  the  quartan  parasite  it  attended  with  fewer 
irregularities  than  that  of  any  other  variety  of  the  malarial  parasite.  Never- 
theless, certain  irregularities  may  occur.  As  pointed  out  by  Antolisei,  seg- 
mentation may  occur  exceptionally  in  pigmented  bodies  considerably  smaller 
than  the  usual  full-grown  forms,  containing  less  pigment  and  filling  only  a 
part  of  the  red  blood  corpuscle.  Here  the  segments  do  not  usually  exceed 
four  to  six  or  eight.  The  accumulation  of  pigment  in  the  segmenting  forms 
may  be  peripheral,  or  distributed  between  the  spores,  or  otherwise  irregular. 

As  the  quartan  parasite  completes  its  development  entirely  within  the 
circulating  blood,  there  is  no  appreciable  difference  at  any  stage  between 
the  splenic  and  the  peripheral  blood  as  regards  the  number  and  variety  of 
the  parasitic  forms  observed.  Moreover  segmenting  forms  of  the  quartan 
parasite  are  often  seen  in  small  number  in  the  blood,  at  a  period  before 
the  total  number  of  organisms  is  sufficiently  large  to  produce  by  their  ripen- 
ing a  paroxysm,  whereas  segmenting  tertian  parasites  are  very  rarely  seen 
in  the  peripheral  blood  without  the  occurrence  of  a  paroxysm  in  relation 
to  the  segmenting  forms. 

Not  all  of  the  mature  forms  proceed  to  sporulation.  Some,  especially 
those  which  may  have  escaped  from  the  red  corpuscles,  swell  up,  become 
transparent  and  larger  than  a  red  blood  corpuscle,  and  present  irregularly 
distributed  and  actively  moving  pigment  granules.    These  swollen,  hydropic 


494  MALAEIA 

forms  are  probably  sterile.  It  can  often  be  seen  in  examining  these  bodies 
in  fresh  blood  that  the  pigment  becomes  quiescent,  the  outlines  of  the  body 
beqome  irregular  and  indistinct,  and  evidently  cadaveric  forms  result.  Or 
these  bodies  may  break  up  into  a  number  of  fragments  which  become  mis- 
shapen and  indistinct,  or  the  whole  body  may  become  vacuolated.  Bodies 
more  or  less  resembling  spores,  but  without  the  nuclear  structure  of  spores, 
may  appear  in  these  vacuoles. 

As  may  occur  with  any  variety  of  the  malarial  parasite,  the  mature  forms 
of  the  quartan  parasite,  instead  of  sporulating,  may  develop  into  flagellate 
bodies  in  the  manner  already  described.  These  bodies  are  smaller  and  con- 
tain coarser  pigment  than  the  flagellate  forms  of  the  tertian  parasite.  De- 
generated and  flagellate  forms  are  less  common  in  quartan  than  in  tertian 
infections. 

Not  only  may  mature  forms  degenerate  in  the  ways  described,  but  forms 
in  earlier  stages  of  development  may  be  liberated  from  the  red  corpuscles 
and  likewise  degenerate. 

The  phenomena  of  phagocytosis  are  observed  with  regularity  during  and 
for  some  hours  after  the  paroxysm  in  quartan  as  well  as  in  other  malarial 
infections.  The  pigment  set  free  by  the  process  of  sporulation  is  taken  up 
by  phagocytes.  Extracorpuscular  organisms,  particularly  the  various  de- 
generated forms,  are  engulfed  by  phagocytes.  The  assault  on  the  flagellate 
bodies  by  leucocytes  can  be  watched  with  interest  on  the  slide  of  fresh  blood. 
The  leucocytes  can  also  be  seen  to  take  up  segmenting  bodies  and  spores  when 
the  specimen  of  blood  is  kept  for  a  while.  The  details  and  the  significance 
of  these  phagocytic  phenomena  will  be  considered  subsequently  (page  519). 

The  intimate  structure  of  the  quartan  and  other  malarial  parasites,  as 
revealed  by  methods  of  staining,  will  also  be  described  subsequently. 

Two  or  more  groups  of  quartan  parasites  are  often  present  in  the  blood  at 
the  same  time,  causing  double  and  triple  quartan  infections.  On  account  of 
the  regularity  in  the  development  of  the  quartan  parasite,  anticipating,  re- 
tarding, and  irregular  fevers  are  less  common  in  quartan  than  in  the  other 
malarial  infections.  Careful  examination  of  the  blood  enables  the  observer 
to  recognize  the  presence  of  two  or  more  groups  of  the  parasite  by  noting  the 
simultaneous  occurrence  of  bodies  in  noticeably  different  stages  of  develop- 
ment; as,  for  example,  during  the  paroxysm  the  association  of  segmenting 
and  young  hyaline  bodies  with  half -grown  pigmented  bodies. 

H.   THE   PARASITE   OF   TERTIAN    FEVER    {IJAEMATOZOON  FEIiRIS   TERTIANAE) 

This  variety  of  tbe  malarial  parasite  is  common  in  most  malarial  regions. 
Where  only  mild  types  of  malaria  occur  it  is,  as  a  rule,  the  prevailing,  and 
sometimes  the  sole,  variety  observed.    The  tertian  and  the  quartan  parasites 


MALARIA  495 

cause  most,  or  in  some  places  all,  of  the  winter  and  spring  intermittents, 
but  they,  and  especially  the  tertian  parasite,  may  cause  in  districts  of  even 
severe  malaria  not  a  few  of  the  malarial  fevers  of  summer  and  autumn, 
although  the  more  severe  and  irregular  of  these  latter  fevers  are  caused 
chiefly  by  the  aestivo-autumnal  parasite.  The  tertian  parasite  may,  how- 
ever, produce  severe,  as  well  as  mild,  types  of  malaria. 

The  tertian  parasite  was  differentiated  from  the  quartan  and  described  in 
its  essential  characters  by  Golgi  in  1886  and  1889.  Other  observers,  par- 
ticularly Antolisei  (1889-90)  and  Bastianelli  and  Bignami  (1890),  have 
added  to,  and  in  some  points  corrected,  Golgi's  first  description. 

The  chief  points  to  be  emphasized  in  this  description  of  the  tertian  para- 
site are  those  which  distinguish  it  from  the  quartan  parasite.  Unlike  the 
quartan  parasite,  certain  stages  of  development  of  the  tertian — namely,  those 
concerned  with  sporulation — take  place  by  preference  in  the  spleen  and  the 
bone  marrow,  although  segmenting  forms  are  seen  also  in  the  peripheral 
blood.    The  cycle  of  development  is  completed  in  forty-eight  hours. 

During  the  paroxysms  or  shortly  after  it  small,  unpigmented,  hyaline, 
amoeboid  bodies  are  found  within  the  red  blood  corpuscles,  of  which  they 
are  about  one-fifth  to  one-fourth  the  size.  Usually  one  hyaline  body  is 
found,  but  not  very  infrequently  two  or  more  are  present,  in  a  single  blood 
corpuscle.  The  tertian  amoebae,  especially  in  their  pigmented  stage,  change 
their  shape  and  position  within  the  corpuscles  much  more  actively  than  the 
quartan  amoebae,  these  movements  being  vigorous  at  ordinary  room  tem- 
perature. Several  branching  pseudopodia  are  sent  out,  often  reaching 
nearly  or  quite  the  periphery  of  the  corpuscle,  and  are  retracted.  All  sorts 
of  shapes  may  thus  be  assumed  by  the  parasite,  which  with  its  long  branch- 
ing processes  may  seem  to  pervade  nearly  the  whole  corpuscle.  By  the  union 
of  two  pseudopodia  the  shape  may  be  that  of  a  ring  enclosing  a  bit  of  the 
corpuscular  substance.  The  tertian  amoebae  are  paler,  less  sharply  outlined, 
than  the  quartan.  In  a  short  time  fine  reddish  brown  or  yellowish  brown 
rods  and  granules  of  pigment,  varying  somewhat  in  size,  appear  in  the 
margins  of  the  amoebae.  Pigment  granules  often  collect  in  the  bulbous 
ends  of  pseudopodia,  and  the  intervening  parts  of  the  pseudopodia  may  be 
so  thin  and  delicate  as  to  be  readily  overlooked,  so  that  the  appearance  may 
he  that  of  several  distinct  bodies  within  one  red  blood  corpuscle.  Careful 
examination  will,  however,  detect  the  fine  connecting  processes  or  the  re- 
traction of  the  apparently  separate  bodies  into  the  substance  of  one  parasite. 
Two  or  more  parasites  may,  however,  be  present  occasionally  within  one  red 
corpuscle.  The  pigment  is  in  finer  grains  and  rods,  and  of  a  lighter,  some- 
what different,  tint  in  the  tertian,  than  in  the  quartan  parasite.  It  is  also  in 
much  more  active  movement  in  the  tertian  amoebae.     This  movement  is 


496  MALARIA 

not  altogether  like  the  Brownian  or  molecular  motion,  and  is  probably  due 
to  intrinsic  protoplasmic  movements  or  currents. 

With  the  continued  growth  and  increased  pigmentation  of  the  amoebae 
the  infected  corpuscles  as  a  rule  become  distinctly  swollen  and  paler  than 
normal —  a  change  which  may  be  already  indicated  even  with  quite  small 
pigmented  forms,  and  which  is  one  of  the  most  distinctive  characters  of  the 
tertian  parasite.  Occasionally  the  enveloping  corpuscle  is  not  noticeably 
swollen  or  altered,  and  exceptionally  it  may  even  shrink  and  acquire  some- 
thing of  the  brassy  appearance  commonly  seen  vtdth  red  corpuscles  infected 
with  aestivo-autumnal  parasite. 

On  the  day  of  apyrexia  the  parasite,  now  with  somewhat  sharper  contour 
and  more  richly  pigmented,  may  attain  a  size  equalling  one-half  to  two- 
thirds  that  of  the  infected  blood  corpuscle.  The  amoeboid  movements  have 
become  more  sluggish,  but  they  persist  in  stages  of  development  correspond- 
ing to  which  forms  of  the  quartan  parasite  have  become  quiescent.  The  pig- 
ment continues  in  active  motion. 

The  fully  developed  parasite  is  about  the  size  of  a  normal  red  corpuscle, 
sometimes  a  little  smaller,  sometimes  somewhat  larger,  and  it  is  therefore 
smaller  than  the  swollen  corpuscle  in  which  it  is  contained.  It  is  nearly  or 
quite  spherical  in  shape,  and  without  amoebic  movements.  The  pigment 
for  a  while  preserves  its  marginal  arrangement  or  less  frequently  is  irregu- 
larly distributed.  The  expanded  red  blood  corpuscle  enveloping  the  parasite 
becomes  still  paler. 

These  fully  grown  forms  change  into  the  presegmenting  bodies  by  the 
collection  of  the  pigment,  which  has  already  become  quiescent  into  a  mass 
of  granules  or  into  a  solid  block  situated  usually  in  or  near  the  center  or 
sometimes  near  or  at  the  margin.  As  with  the  other  varieties  of  the  mala- 
rial parasite,  the  pigment  with  the  development  of  the  parasite  becomes 
coarser,  and  the  delicate  rod-like  forms  of  pigment  become  relatively  less 
numerous.  These  spherical  bodies  with  central  pigment  clumps  are  more 
refractive  than  is  the  parasite  in  preceding  stages  of  development.  Stained 
specimens  show  that  in  these  presegmenting  bodies  there  appear  multiple, 
deeply  staining  chromatin  granules,  which  represent  nuclear  substance, 
and  which  are  the  first  indication  of  the  inception  of  sporulation. 

This  phase  of  segmentation  presents  more  variation  than  is  observed  in 
the  quartan  parasite.  Sometimes  it  begins  with  the  appearance  of  radial 
striation  extending  from  the  periphery  to  the  center,  and  proceeds  by  a  divi- 
sion of  the  substance  of  the  parasite  into  twelve  to  twenty  or  even  more  seg- 
ments arranged  in  a  rosette  form  around  the  central  clump  of  pigment.  A 
little  later  the  pigment  clump  is  surrounded  by  a  group  of  small  round 
bodies,  which  are  the  spores.     More  commonly,  without  the  formation  of 


MALAEIA  497 

such  regular  figures,  the  protoplasm  breaks  up  into  a  mass  of  fourteen  to 
twenty  or  more  spores.  Sometimes  one  sees  an  outer  and  inner  ring  of 
spores  concentrically  arranged  around  the  central  mass  of  pigment.  The 
larger  number  of  segments  or  spores  formed  by  the  tertian  as  contrasted 
with  the  quartan  parasite  is  an  important  differential  characteristic. 

The  modes  of  segmentation  described  correspond  in  the  main  to  Golgi's 
second  type  of  segmentation.  His  first  mode  of  segmentation  of  the  tertian 
parasite  has  not  been  noted  by  other  observers.  It  is  as  follows :  After  the 
collection  of  the  pigment  in  the  centre  the  organism  is  differentiated  into  a 
peripheral  zone  sharply  separated  from  a  central  body  containing  the  pig- 
ment. The  peripheral  ring  becomes  radially  striated,  and  then  divides 
into  fifteen  to  twenty  small  hyaline  segments.  The  central  pigmented  body 
does  not  segment,  but  remains  behind  after  the  separation  of  the  spores. 
Golgi's  third  variety  of  segmentation  is  now  generally  recognized  as  a  process 
of  degenerative  vacuolation. 

Sometimes  the  segmenting  bodies  show,  instead  of  one  central  accumu- 
lation of  pigment,  two  or  more  clumps  excentrically  placed,  or  the  pigment 
may  be  concentrated  in  the  periphery  or  distributed  between  the  spores  or 
otherwise  irregularly  arranged. 

The  spores  are  set  free  by  rupture  of  the  enveloping  membrane  derived 
from  the  red  corpuscles,  or  this  membrane  may  have  disappeared  before  the 
segmentation  is  completed.  The  individual  spores  are  somewhat  smaller 
than  those  of  the  quartan  parasite.  They  usually  show  a  refractive  nuclei- 
form  dot,  which  is,  as  a  rule,  less  distinct  than  in  the  quartan  spores. 

Coincidently  with  sporulation  the  young  colorless,  amoebae,  formed  from 
the  spores,  make  their  appearance  in  the  red  blood  corpuscles  and  start  on 
a  fresh  cycle  of  development. 

The  segmenting  bodies  may  make  their  appearance  several  hours  before 
the  paroxysm.  They  are  most  numerous  shortly  before  and  during  the 
onset  of  the  paroxysm.  They  may  be  scanty  in  the  peripheral  blood,  for 
the  process  of  sporulation  takes  place  largely  in  the  internal  organs.  The 
red  corpuscles  containing  mature  and  presegmenting  bodies  accumulate 
especially  in  the  spleen  and  the  bone  marrow,  and  there  the  organisms  com- 
plete their  reproductive  development.  During  most  of  the  period  of  apyrexia 
no  noticeable  difference  is  observed  in  the  number  and  kinds  of  parasites 
between  the  peripheral  blood  and  that  withdrawn  by  hypodermic  syringe 
from  the  spleen.  But  shortly  before  and  during  the  paroxysm  far  more  ripe 
and  sporulating  forms  are  found  in  the  splenic  than  in  the  peripheral  blood. 

Precocious  segmentation  into  five  to  ten  spores  may  occur  in  bodies, 
sometimes  containing  only  a  grain  or  two  of  pigment,  which  have  not 
attained  a  size  exceeding  one-half  to  two-thirds  that  of  the  red  blood 


498  MALAEIA 

corpuscles,  the  usual  size  of  a  segmenting  body  being  about  that  of  a  red 
corpuscle,  but  sometimes  considerably  larger.  Such  immature  forms  of  seg- 
mentation are  associated  by  Bastianelli  and  Bignami  with  anticipating 
fevers,  but  ]\Iannaberg  and  Thayer  and  Hewetson,  although  not  inclined  to 
discredit  this  interpretation,  were  unable  to  convince  themeslves  of  this 
relation. 

Partly  developed  and  mature  tertian  parasites  are  often  seen  free  in  the 
plasma.  Swollen,  transparent,  extracorpuscular  forms  which  may  attain 
the  size  of  large  leucocytes,  and  which  contain  scattered  dancing  pigment 
granules,  are  generally  considered  to  be  degenerative  or  incapable  of  repro- 
ductive development.  These  so-called  hydropic  forms  are  considerably 
larger  and  paler  and  more  common  than  the  similar  forms  of  the  quartan 
parasite.  These  swollen,  richly  pigmented  forms  are  very  common  in  tertian 
infections.  In  general,  the  various  forms  of  degeneration  which  have 
already  been  described,  such  as  fragmentation,  vacuolation,  pseudo-gem- 
mation, are  more  common  with  the  tertian  than  the  quartan  parasite.  Flag- 
ellate bodies  are  likewise  more  common.  They  are,  as  a  rule,  larger  and 
contain  finer  pigment  than  the  quartan  flagellates.  They  develop  chiefly 
from  the  round,  swollen,  extracorpuscular  forms  with  scattered  pigment, 
although  flagella  have  been  observed  to  develop  from  forms  still  surrounded 
with  a  distinct  layer  of  hemaglobin  containing  substance  of  the  red  blood 
corpuscle.  Flagellate  bodies  are  most  abundant  in  blood  withdrawn  from 
the  spleen  shortly  before  and  during  the  paroxysm.  Phagocytosis  occurs 
with  the  same  regularity  and  with  similar  phenomena  in  tertian  as  in 
quartan  infections. 

Infection  with  two  groups  of  tertian  parasites  (double  tertian),  as  des- 
cribed for  quartan  infection,  is  more  common  than  with  a  single  group, 
especially  in  the  later  period  of  the  malarial  season  in  the  spring  and  in 
summer  and  autumn.  The  resulting  type  of  fever  is  quotidian.  In  some 
cases  there  seem  to  be  several  irregularly  distributed  generations  causing 
remittent  or  subcontinued  fevers.  It  is  not  necessary  to  attribute  the  pres- 
ence of  two  or  more  groups  of  the  same  variety  of  parasite  to  corresponding 
multiple  infections  from  without.  There  is  evidence  that  certain  members 
of  a  group  may,  in  their  development,  lag  behind  or  advance  beyond  others 
of  the  same  grouj),  and  in  course  of  time  by  further  multiplication  may  con- 
stitute a  separate  group  capable  of  causing  its  own  paroxysms  of  fever.  It 
is  remarkable,  however,  that  the  second  group  should  be  separated  in  its 
cycle  of  development  by  such  definite  intervals  from  the  first  as  we  usually 
observe  in  quotidian  fevers  of  tertian  origin.  Genuine  mixed  infections  with 
malarial  parasites,  the  most  frequent  combination  being  that  of  the  tertian 
and  of  the  aestivo-autuninal  parasites,  are  not  very  uncommon. 


MALAEIA  499 

The  length  of  the  cycle  of  development  of  the  tertian  parasite  may  occa- 
sionally be  noticeably  shorter  than  forty-eight  hours,  perhaps  only  forty 
hours  or  less,  or,  on  the  other  hand,  it  may  be  longer  than  the  normal  period. 
This  may  explain  the  anticipating  and  the  postponing  fevers. 

III.   THE    PARASITE    OF    AESTIVO-AUTLTMNAL   FEVER    {BAEMATOZOON   FALCIPARUM) 

This  was  first  clearly  differentiated  from  other  varieties  ot  the  malarial 
parasite  by  Marchiafava  and  Celli  (1889),  and  was  subsequently  more  fully 
described  by  the  same  authors  and  by  Canalis  (1889-90).  (See  footnote, 
page  481.)  The  extensive  literature  concerning  the  parasitology  of  malaria 
during  the  last  six  years  has  been  concerned  to  a  large  extent  with  this 
variety,  but  we  are  still  far  from  possessing  so  full  and  accurate  knowledge 
regarding  the  characters  and  development  of  Haematozoon  falciparum  as 
regarding  those  of  the  quartan  and  tertian  parasites.  Such  knowledge  is 
much  to  be  desired  in  view  of  the  frequency  of  the  aestivo-autumnal  parasite 
in  regions,  such  as  the  southern  part  of  the  United  States,  where  the  more 
severe  types  of  malaria  occur,  and  of  the  almost  exclusive  association  of  this 
parasite  with  pernicious  malarial  fevers. 

Chief  reasons  for  the  difficulty  in  investigating  the  entire  life  history  of 
Haematozoon  falciparum  are  that  it  develops  mainly  within  the  internal 
organs  and  often  in  multiple  groups,  and  that  the  later  reproductive  phases 
of  development  are  met  with  in  the  circulating  blood  only  very  exceptionally. 
Under  the  Classification  of  the  malarial  parasites  we  have  already  presented 
the  more  imjwrtant  opinions  which  have  been  advanced  concerning  possible 
subdivisions  of  the  aestivo-autumnal  variety  (page  484  et  seq.). 

The  youngest  forms  of  this  parasite  are  small  hyaline  bodies,  about  one- 
sixth  the  diameter  of  a  red  blood  corpuscle,  which  make  their  appearance  in 
the  blood  corpuscles  during  or  shortly  after  the  parox3'Sm.  It  is  not  uncom- 
mon to  find  two  or  more  hyaline  bodies  in  a  single  corpuscle.  The  aestivo- 
autumnal  hyaline  bodies  are  in  general  the  smallest  forms  of  the  malarial 
parasite  which  are  observed  in  the  red  blood  corpuscle.  The  youngest  forms 
may  be  quiescent,  but  as  they  develop  they  manifest  amoeboid  movements 
resembling  in  their  activity  those  of  the  tertian  amoebae. 

The  young  aestivo-autumnal  amoebae  may  not  be  readily  distinguishable 
from  the  similar  forms  of  the  quartan  and  tertian  parasites.  Particularly 
characteristic,  however,  the  young  hyaline  forms  of  Haematozoon  falciparum 
when  in  repose  and  in  stained  specimens  is  the  ring  shape.  The  appearance 
in  fresh  specimens  is  that  of  a  somewhat  refractive,  clear,  hyaline  ring, 
usually  thicker  on  one  side,  surrounding  a  small  round  central,  or  oftener 
excentric,  shaded  part,  or  sometimes  two  or  three  such  parts,  through  which 
the  color  of  the  red  corpuscle  shows.    In  stained  specimens  the  ring  appears 


500  MALAEIA 

thinner  than  in  fresh  specimens,  and  the  central  or  oftener  excentric  part  is 
unstained,  wliile  a  minute  deeply  stained  granule  is  situated  in  the  outer  ring. 

The  study  of  the  further  development  of  these  forms,  especially  on 
stained  specimens,  has  demonstrated  that  these  apparently  annular  bodies 
are  not  actual  rings,  as  some  have  supposed,  enclosing  a  bit  of  the  red  cor- 
puscle, but  that  the  clear  area  which  does  not  stain  is  a  transparent  part  of 
the  organism,  which,  as  will  be  subsequently  explained,  some  regard  as  the 
nucleus.  Actual  rings,  however,  as  has  already  been  mentioned,  may  be 
formed  by  the  junction  of  pseudopodia,  which  thereby  enclose  some  of  the 
corpuscular  substance,  but  such  is  not  the  explanation  of  the  typical  annular 
appearance  of  the  aestivo-autumnal  hyaline  bodies.  It  is  not  uncommon  to 
find  free  hyaline  bodies  in  the  blood  plasma. 

These  hyaline  bodies  may,  while  under  observation,  become  somewhat 
expanded  and  paler  and  lose  their  annular  appearance,  and  again  resume 
the  ring  shape.  While  the  very  smallest  intracorpuscular  hyaline  bodies 
may  present  no  amoeboid  movements,  as  they  grow  larger  these  movements 
become  active.  Hyaline  bodies  are  occasionally  observed  to  change  their 
position  within  the  corpuscle  without  change  in  their  shape.  Manifold 
shapes  are  assumed  during  the  amoeboid  movements. 

Usually  in  the  course  of  development  a  few  very  fine  dark  reddish  brown 
or  black  pigment  granules  appear  in  the  outer  layer  of  the  hyaline  bodies. 
They  may  be  situated  near  the  periphery  or  on  the  inner  margin  of  the  ring 
near  the  clear  part.  Sometimes  the  pigment  does  not  appear  until  shortly 
before  a  paroxysm.  Tlie  presence  of  many  bodies  containing  a  considerable 
number  of  grains  of  pigment  is  generally  indicative  of  an  impending  par- 
oxysm. The  pigment  granules  are  at  first  very  minute  and  few,  and  may 
be  readily  overlooked.  The  granules  of  pigment  increase  in  number  and  size, 
but  it  is  one  of  the  characteristics  of  the  aestivo-autumnal  amoebae  that  the 
formation  of  pigment  is,  as  a  rule,  scanty  and  in  fine  grains.  Often  only 
one  or  two  very  fine  pigment  granules  are  seen  in  the  periphery  or  on  the 
inner  edge  of  the  refractive  border  of  the  hyaline  bodies.  Usually  about 
six  or  seven  granules  of  pigment  are  developed  in  the  hyaline  bodies.  The 
pigment  generally  shows  but  little  motion  in  contrast  with  that  in  the  tertian 
amoebae. 

The  aestivo-autumnal  amoeboid  forms  do  not  generally  grow  larger  than 
one-quarter  to  one-third  the  diameter  of  the  red  blood  corpuscle,  and  they  may 
remain  smaller.  The  infected  red  corpuscles  may  appear  otherwise  normal. 
They  do  not  become  swollen  and  decolorized  in  this  stage,  as  is  the  case  in 
the  tertian  infections.  On  the  other  hand,  they  often  become  shrunken, 
creased,  or  otherwise  deformed,  and  present  a  deep  brassy  color  {globuli 
rossi  ottonati  of  the  Italian  writers).    Sometimes  the  haemoglobin  separates 


MALAEIA  501 

from  a  part  or  the  whole  of  the  outer  part  of  the  stroma  of  the  corpuscle  and 
collects  around  the  enclosed  hyaline  body.  These  changes  in  the  red  cor- 
puscles, which  are  particularly  characteristic  of  the  aestivo-autumnal  variety, 
although  not  absolutely  limited  to  it,  are  to  be  regarded  as  degenerative  or 
necrobitic.  Marchiafava  and  Celli  and  some  others  have  thought  tliat  the 
parasite  within  these  profoundly  altered  corpuscles  is  also  dead  or  incapable 
of  further  development.  Bastianelli  states  that  sporulation  forms  are  not 
observed  in  the  brassy  corpuscles,  but  this  statement  is  opposed  to  observa- 
tions of  Marchiafava  and  Bignami  and  others.  The  view  that  parasites 
within  profoundly  altered  corpuscles  are  "incapable  of  further  development 
is  by  no  means  proven,  and  is  opposed  to  the  natural  interpretation  of  many 
observations. 

As  the  time  for  the  onset  of  a  paroxysm  approaches,  the  hyaline  bodies 
gradually  cease  their  amoeboid  movements,  assumie  a  spherical  or  ovoid 
shape,  become  somewhat  more  refractive  and  homogeneous,  and  present  a 
small  collection  of  quiescent  or  but  slightly  moving  pigment  granules  at 
about  the  centre  or  often  near  the  periphery.  This  pigment  usually  fuses 
into  a  single  small,  black,  round  or  irregular  mass  or  block,  or  there  may  be 
two  such  blocks. 

These  round,  refractive  bodies  with  pigments  blocks  or  collections  of 
pigment  granules  {corpi  con  blocchetto)  are  the  presegmenting  bodies,  and 
when  they  are  present  the  onset  of  a  paroxysm,  within  at  most  a  few  hours, 
may  generally  be  safely  predicted.  These  bodies  are  much  smaller  than  the 
corresponding  forms  of  the  quartan  and  tertian  parasites.  They  do  not 
generally  exceed  one-quarter  or  one-third  of  the  size  of  the  corpuscle,  al- 
though they  may  be  considerably  larger.  They  are  surrounded  with  haemo- 
globin containing  substance  of  the  corpuscle,  which  is  often  of  a  brassy  color. 

The  next  phase  of  development  is  that  of  sporulation,  but  the  segmenting 
forms  are  found  in  the  peripheral  blood  only  most  exceptionally,  save  in 
some  pernicious  cases,  in  which  they  may  in  rare  instances  be  even  abundant. 
Sacharoff  observed  in  the  Transcaucasus  sporulating  forms  in  the  blood,  and 
on  this  account,  but  apparently  without  sufficient  reason,  he  regards  this 
form  as  a  special  variety.  For  a  few  hours  before  and  during  the  early  stage 
of  the  paroxysm  very  few  parasitic  forms  of  any  kind  are  to  be  found  in  the 
circulating  blood,  and  at  this  period  they  may  be  entirely  absent,  in  marked 
contrast  to  quartan  infection.  During  this  period  the  presence  of  pigmented 
leucocytes  in  the  blood  may  aid  in  the  diagnosis.  In  tertian  infections  an 
analogous  condition  is  found,  but  not  in  the  same  degree.  The  disappearance 
of  the  parasites  from  the  blood  is  believed  by  most  authorities  to  be  due  to 
their  deposition  in  internal  organs,  especially  the  spleen  and  the  bone 
marrow,  and  is  attributed  to  the  profound  changes  in  the  red  blood  corpuscles 


502  MALAEIA 

containing  them,  these  changes  rendering  the  corpuscles  virtually  foreign 
bodies  which,  like  other  foreign  particles,  are  caught  and  retained  especially 
in  the  spleen  and  the  bone  marrow. 

Blood  withdrawn  by  puncture  of  the  spleen  at  this  time  will,  with  rare 
exceptions,  show  abundant  intracorpuscular  and  free  round  bodies  with 
central  or  peripheral  pigment,  and  also  segmenting  forms.  In  certain 
cases  segmenting  forms  are  few  in  the  spleen,  but  abimdant  in  certain  other 
internal  organs,  as  has  been  shown  by  postmortem  examinations.  These 
sporulating  bodies  are  smaller  than  those  of  the  quartan  and  tertian  parasites, 
and  occupy,  as  a  rule,  only  a  relatively  small  part  of  the  corpuscle,  which  is 
always  altered  in  appearance,  being  shrunken  and  brassy  colored  or  more 
frequently  decolorized.  They  may  appear  to  be  free  or  may  be  actually  free. 
In  pernicious  cases  they  are  present  in  large,  often  enormous,  numbers  in 
the  internal  organs,  especially  in  the  spleen  and  bone  marrow,  and  in  some 
types  of  pernicious  fever  in  the  capillaries  of  the  brain  and  in  those  of  the 
intestinal  mucosa.  This  varied  distribution  of  the  parasites  in  internal 
organs  is  in  relation  with  the  types  of  pernicious  fever.  The  stage  of  sporu- 
lation  occupies  a  rather  long  period  and  takes  place  in  successive  groups. 
This  circumstance  is  believed  to  explain  the  long  duration  of  the  paroxysm 
in  aestivo-autumnal  fevers.  In  pernicious  cases  sporulation  seems  to  be 
going  on  continually  in  the  vascular  areas  of  certain  internal  organs. 

In  aestivo-autumnal  infections  the  process  of  sporulation  is  in  general 
similar  to  that  of  the  tertian  parasite,  but  it  is  more  irregular  and  variable 
and  the  spores  are  much  smaller.  The  number  of  spores  formed  by  a  seg- 
menting aestivo-autimmal  organism  is  extremely  variable.  There  may  be 
not  more  than  six  to  ten  spores,  or  even  fewer ;  often  there  are  ten  to  twenty, 
and  the  number  may  exceed  thirty.  Some  segmenting  forms  are  much  larger 
than  others.  Golgi  has  observed  exceptionally  very  large  ones  containing  as 
many  as  forty  to  fifty  spores.  There  are  slight  differences  often  to  be  ob- 
served in  the  finer  structure  between  the  aestivo-autumnal  spores  and  those 
of  the  quartan  and  tertian  parasites,  as  will  be  described  when  we  consider 
the  intimate  structure  of  the  malarial  parasites. 

The  young  hyaline  bodies  of  the  new  generation  may  be  found  in  the  blood 
in  the  early  part  of  the  paroxysm,  but  often  they  do  not  make  their  appearance 
until  several  hours  after  the  beginning  of  the  paroxysm  or  during  its  decline. 

Not  all  of  the  aestivo-autumnal  amoebae  develop  pigment.  Sporulation 
may  occur  in  bodies,  usually  of  small  size,  entirely  devoid  of  pigment.  As 
a  rule  in  these  cases  both  pigmented  and  unpigmented  forms  occur,  but  cases 
of  aestivo-autumnal  malaria  have  been  observed,  especially  in  tropical  cli- 
mates, in  which  only  unj)igmentcd  bodies  could  be  found  at  any  stage  of  tlie 
fever  before  the  a{)pearance  at  a  later  period  of  crescentic  bodies  which  always 
contain  pigment. 


MALAEIA  503 

As  has  already  been  mentioned  (page  487)  Grassi  and  Feletti  regard  the 
parasites  which  do  not  develop  pigment  as  belonging  to  a  distinct  variety 
(Haemamoeha  immaculata) ,  but  it  is  difficult  to  reconcile  this  view  with 
the  frequent  association  of  pigmented  and  unpigmented  forms,  the  frequent 
transitions  from  one  to  the  other  as  regards  the  quantity  of  pigment  de- 
veloped, and  the  absence  of  any  points  of  distinction  other  than  the  presence 
or  absence  of  a  variable,  but  generally  small,  amount  of  pigment.  Still 
further  researches,  especially  of  the  grave  tropical  malarias,  may  perhaps 
demonstrate  the  existence  of  a  distinct  unpigmented  variety  of  the  parasite. 

There  is  considerable  uncertainty  as  to  the  length  of  the  cycle  of  develop- 
ment of  Haematozoon  falciparum.  This  uncertainty  is  due  to  the  manner 
of  development  of  the  parasite,  usually  in  multiple  groups,  in  the  internal 
organs,  the  most  characteristic  reproductive  phases  being  absent  from  the 
circulating  blood.  So  far  as  one  can  judge  from  the  study  of  these  phases 
in  connection  with  the  different  types  of  fever  with  which  they  may  be  asso- 
ciated, the  length  of  the  cycle  of  development  may  vary  from  twenty-four 
hours  or  less  to  forty-eight  hours  or  more. 

Haematozoon  falciparum,  may  be  associated  with  typical  quotidian  fever 
or  with  tertian  fever,  and  in  some  of  these  cases  the  blood  shows  apparently 
only  one  group  of  organisms.  As  already  mentioned,  Marchiafava  and  Big- 
nami  believe  that  there  are  two  distinct  varieties  or  subvarieties  of  the 
aestivo-autumnal  parasite,  the  one  a  true  quotidian  organism,  with  a  cycle 
of  twenty-four  hours'  duration,  and  the  other  their  so-called  malignant  or 
summer-autumn  tertian  variety,  with  a  cycle  of  forty-eight  hours'  duration ; 
and  this  division  has  been  accepted  by  some  other  authors.  This  distinction 
is  based  mainly  upon  the  apparent  duration  of  the  cycle  of  development — 
in  the  quotidian  about  twenty-four  hours,  and  in  the  malignant  tertian 
forty-eight  hours,  more  or  less — but  there  are  claimed  to  be  other  differences 
of  a  minor  character  relating  to  the  pigmentation,  the  size,  and  the  amoeboid 
movements  of  the  organisms.''''    The  differential  diagnosis  is  said  to  be  pos- 

^'  The  following  are  the  biological  axid  morphological  differences  between  the 
aestivo-autumnal  quotidian  and  malignant  tertian  parasites,  according  to  Mar- 
chiafava and  Bignami  (On  Summer-Autumn  Malarial  Fevers,  translation,  p.  83, 
The  New  Sydenham  Society,  London,  1894):  Duration  of  cycle  development  in 
the  quotidian,  about  twenty-four  hours,  in  the  summer  tertian,  forty-eight  hours, 
more  or  less;  in  the  quotidian  sporulation  on  rare  occasions  is  completed  before 
the  amoebae  have  become  pigmented — this  is  not  observed  in  the  summer  tertian; 
the  fine  granules  of  pigment  in  the  periphery  of  the  summer  tertian  are  some- 
times endowed  with  oscillatory  movements — this  is  not  noticed  in  the  quotidian; 
in  the  same  relative  stage  of  development  the  tertian  amoeba  is  usually  larger 
than  the  quotidian,  the  adult  pigmented  tertian  forms  may  be  one-third  of  the 
size  of  the  red  blood  corpuscles,  and  the  forms  of  segmentation  may  be  one-half  or 


504  MALARIA 

Bible  only  with  the  adult  forms.  The  differential  characters  claimed  to  exist 
between  the  quotidian  and  the  tertian  varieties  of  the  aestivo-autumnal 
parasite  are,  for  the  most  part,  only  such  as  one  would  expect  with  a 
malarial  parasite  developing  more  rapidly  in  some  cases  than  in  others,  and 
they,  at  least  so  far  as  at  present  formulated,  scarcely  suffice  for  a  distinction 
into  two  well  defined  varieties. 

Thayer  and  Hewetson,  while  confirming  Marchiafava  and  Bignami's 
recognition  of  quotidian  and  tertian  fevers  caused  by  the  aestivo-autumnal 
parasite,  emphasize  the  occurrence  of  intermediate  types  of  fever,  and  in 
general  the  essential  irregularity  of  the  fevers  caused  by  this  organism. 
They  were  unable  to  distinguish  any  morphological  or  biological  differences 
between  the  parasites  associated  with  these  various  types  of  fever.  Although 
unwilling  to  commit  themselves  to  a  positive  conclusion,  they  are  "  inclined 
to  believe  that  the  irregularity  of  the  febrile  manifestations  is  due  chiefly 
to  the  tendency  on  the  part  of  the  parasite  to  irregularities  in  the  length  of 
its  cycle  of  development  (this  variability  being  dependent,  perhaps,  upon 
the  malignity  of  the  organism  or  upon  the  resistance  of  the  individual 
affected)  ;  to  the  fact  that  the  period  of  time  required  for  the  sporulation  of 
one  group  of  organisms  is  materially  greater  than  in  the  regular  infections, 
owing  to  the  fact  that  the  arrangement  of  the  parasites  in  definite  sharp 
groups,  sporulating  nearly  at  the  same  time,  is  much  less  distinct  than  in 
the  tertian  and  quartan  intermittents ;  to  the  fact  that,  frequently,  organisms 
in  all  stages  of  development  are  present  at  one  time,  segmentation  occurring 
almost  continuously.*'  ** 

Golgi  also  considers  that  Marchiafava  and  Bignami's  division  into  quoti- 
dian and  tertian  aestivo-autumnal  organisms  is  based  upon  insufficient 
evidence,  and  that  the  duration  of  the  cycle  of  development  of  the  aestivo- 
autumnal  parasite  is  indeterminate,  or  at  least  has  not  as  yet  been  accurately 
ascertained.  This  cycle  is  probably,  he  thinks,  longer  than  is  supposed  by 
Marchiafava  and  Bignami.  This  form  of  parasite,  according  to  Golgi,  is 
characterized  by  the  fact  that  it  develops  entirely  in  the  internal  organs,  and 
that  the  forms,  chiefly  of  the  earlier  stages  of  development,  which  appear  in 
the  circulation,  although  they  are  found  there  at  certain  periods  of  the  dis- 

two-thirds  of  it;  in  the  tertian  tiie  amoeboid  movements  are  maintained  longer, 
even  in  the  adult  pigmented  forms,  and  the  motion  is  more  lively  than  in  the 
quotidian  during  the  pigmented  phase;  the  duration  of  the  non-pigmented  amoe- 
boid phase  in  the  tertian  is  relatively  long  and  may  exceed  twenty- four  hours;  the 
young  forms  of  the  new  generation  in  the  tertian  usually  appear  in  the  blood 
several  hours  after  the  beginning  of  the  paroxysm,  which  is  much  later  than  in 
the  quotidian. 

"Op.  cit.,  pp.  151.  153. 


MALARIA  505 

ease  in  practically  all  cases,  are,  in  a  sense,  accidentally  present  in  this  situa- 
tion, being  washed  into  the  circulation  from  their  foci  of  development,  as 
nucleated  red  blood  corpuscles  may  be  conveyed  from  the  bone  marrow  into 
the  blood  current  in  certain  anaemias.  Golgi  at  first  thought  that  the  forms 
present  in  the  circulation  degenerate,  but  he  does  not  now  deny  that  they 
may  lodge  in  internal  organs  and  there  develop  into  segmenting  organisms. 
Marchiafava  and  Bignami  with  much  reason  vigorously  contest  Golgi's 
conception  of  the  "  accidental "  nature  of  the  presence  of  aestivo-autumnai 
organisms  in  the  circulating  blood,  although  they  also  believe  that  a  large 
part  of  the  parasites  develop  wholly  in  the  internal  organs,  and  that  sporula- 
tion  occurs  only  most  exceptionally  in  the  circulating  blood. 

The  two  most  important  and  original  points  in  Golgi's  doctrine  concern- 
ing the  aestivo-autumnai  parasite  are  that  groups  of  the  parasitic  organisms 
are  variously  distributed  in  vascular  areas  in  the  internal  organs,  and  there 
develop  more  or  less  independently  of  each  other,  "  with  relative  stability," 
and  that  a  large  number  of  the  organisms  develop  within  leucocytes,  endo- 
thelial cells,  and  other  tissue  cells.  All  phases  of  development,  according  to 
Golgi,  are  found  within  these  cells.  The  spleen  and  the  bone  marrow  are 
situations  preferred  by  the  parasite,  but  the  capillaries  of  the  liver,  of  the 
brain,  of  the  lungs,  of  the  intestinal  mucosa,  may  also  contain  them  enclosed 
within  cells. 

A.  Monti "  has  recently  described  these  intracellular  forms  in  pernicious 
malaria,  and  he  confirms  the  observation  of  many  others  that  cells  containing 
parasites  frequently  degenerate  and  die.  He  finds  apparently  intact  parasites 
not  infrequently  within  cells,  particularly  endothelial  cells. 

It  is  contended  by  Marchiafava,  Bignami,  and  Bastianelli  that  the  intra- 
cellular inclusions  of  the  parasite,  upon  which  Golgi  bases  his  doctrine,  are 
simply  the  well  known  phagocytic  phenomena,  and  that  such  enclosed  para- 
sites belong  chiefly  to  the  later  stages  of  development  ( presegmenting  and 
segmenting  bodies  and  spores),  and  that,  instead  of  developing,  they  de- 
generate within  the  cells.  The  young  amoeboid  bodies,  which,  according  to 
Golgi's  doctrine,  should  be  frequently  found  within  cells,  they  found  only 
with  comparatively  infrequency  within  phagocytes,  and  then  almost  always 
within  their  corpuscular  hosts,  which  had  been  swallowed  by  cells.  They 
admit  the  possibility  of  some  development  of  intracorpuscular  parasites 
which  have  been  taken  up  by  phagocytes,  but  not  of  free  parasites  within 
cells. 

As  with  the  other  varieties  of  the  malarial  parasite,  the  aestivo-autumnai 
do  not  all  mature  and  segment.    Extracorpuscular  forms  are  common,  and 

='^  A.  Monti:    Bollettino  della  Society  medico-chirurgica  di  Pavia,  1895. 
35 


506  MALARIA 

it  is  more  jmrtiiularl}'  these  ionns,  deprived  of  the  protective  covering  of  the 
red  blood  corpuscles,  which  degenerate.  Adult  and  presegmenting  bodies 
and  bodies  of  tiie  crescentic  phtuse  frequently  become  swollen  and  pale  or 
vacuolated  or  fragmented,  or  throw  off  buds,  or  present  other  degenerative 
changes  which  have  been  described. 

riiagocytism  in  the  aestivo-autuninal,  as  in  all  malarial  infections,  is  a 
phenomenon  of  much  importance,  as  will  be  subsequently  explained. 

The  frequency  with  which  two  or  more  groups  of  parasites  in  different 
Btages  of  develo})nu'nt  are  found  in  aestivo-autumnal  infections  has  already 
been  repeatedly  emphasized.  Marchiafava  and  Bignami  believe  that  even 
in  the  pernicious  fevers  there  are  not  generally  present  more  than  two  groups 
of  the  aestivo-autumnal  parasite,  and  that  the  short  cycle  of  development  and 
the  prolonged  period  of  sporulation  suilice  to  explain  the  simultaneous  pres- 
ence of  parasites  in  notably  different  stages  of  development.  Combined  in- 
fections with  the  aestivo-autumnal  parasite  and  one  of  the  other  varieties 
occasionally  occur. 

It  is  important  to  bear  in  mind  the  discrepancy  which  characterizes 
aestivo-autumnal  malaria  between  the  number  of  parasites  in  the  blood  and 
the  number  in  the  internal  organs.  In  the  majority  of  cases  th«  more  severe 
the  infoction  the  greater  the  number  of  parasites  found  in  the  circulating 
blood,  but  there  are  so  many  exceptions  to  this  that  the  number  of  parasites 
in  the  blood  cannot  be  corrsidered  a  trustworthy  index  of  the  number  within 
the  body.  Pernicious  cases  have  been  repeatedly  observed  where  the  splenic 
blood  examined  during  life  or  the  internal  organs  examined  after  death 
contained  enormous  numbers  of  aestivo-autumnal  parasites,  although  the 
blood  of  the  finger  showed  very  few.  The  organisms  may  be  few  even  in  the 
spleen  when  they  are  abundant  in  the  cerebral  capillaries  or  in  some  other 
situation.  As  will  be  explained  subsequently,  the  varying  symptoms  and 
types  of  pernicious  malaria  can  lie  explained  in  large  part  by  the  varying 
distribution  of  the  parasites  in  internal  organs. 

It  is  evident  from  the  description  which  has  hecn  given  of  the  aestivo- 
autumnal  parasite  that  this  variety  is  characterized  especially  by  its  great 
activity  in  multiplication,  and  it  will  appear  from  the  consideration  of  the 
clinical  features  of  the  infections  caused  by  this  parasite  that  other  most 
importiuit  characteristics  are  its  virulence,  greater  than  that  of  other  varie- 
ties, and  its  greater  resistance  to  (piiiiine. 

There  is  a  grouj)  of  bodies  of  crescentic,  fusiform,  oval,  or  round  shape, 
prescHting  certain  common  and  peculiar  characters,  which  develoj)  only  from 
Ilaematozoon  faliciparutn.  The  crescents  are  the  most  typical  of  tliese 
bodies,  which  may  be  designated,  therefore,  as  bodies  of  the  crescentic  (or 
semilunar)  j)hase  or  group.    They  merit  special  consideration. 


MALARIA  507 

Bodies  of  the  (Jrescentic  Group. — Wlien  a  malarial  fever  caused  by  Haerna- 
tozoon  falciparum  ha.s  lasted  a  week  or  more  bodies  of  the  crescentic  or 
semilunar  phase  are  likely  to  appear  in  tlie  blood.  They  are  very  rarely 
found  in  tlie  blood  in  the  latter  part  of  the  first  week.  If  the  fever  is  treated 
with  sufficient  doses  of  quinine  during  the  early  part  of  the  first  week,  cres- 
cents do  not  appear,  but  the  administration  of  quinine  after  the  fever  has 
lasted  much  longer  than  a  week  does  not  prevent  their  appearance.  They 
may  persist  in  the  blood  two  weeks  or  more  after  all  other  forms  of  the  para- 
site have  disappeared.  In  such  cases  they  are  often  unassociated  with  any 
febrile  manifestations  or  any  symptoms  which  can  be  definitely  referred  to 
their  presence.  If  a  relapse  of  the  fever  occurs,  then  the  young  hyaline 
bodies  already  described  are  always  present.  The  crescents  themselves  are 
very  resistant  to  the  action  of  quinine.  Councilman  in  1887  called  attention 
to  the  occurrence  of  crescentic  bodies  as  characteristic  of  the  irregular  and 
remittent  forms  of  malarial  fever  and  malarial  cachexia. 

There  was  for  a  time  much  doubt  as  to  the  origin  of  the  crescents,  but 
Marchiafava  and  Celli's  demonstration  in  1886  of  their  intracorpuscular 
development  has  been  abundantly  confirmed  by  the  later  studies  of  Canalis, 
Bastianelli  and  Bignami,  and  others.  The  early  intracorpuscular  stages  of 
development  of  the  bodies  of  the  crescentic  group  are  rarely  seen  in  the  cir- 
culating blood,  except  in  certain  pernicious  cases,  but  they  can  often  be 
found  in  the  splenic  blood.  Bastianelli  and  Bignami  have  found  these  early 
phases  so  abundantly  in  the  bone  marrow  that  they  consider  that  they  de- 
velop by  preference  in  this  situation. 

Certain  of  the  intracorpuscular  spherical  forms  of  Haematozoon  falci- 
parum with  collected  pigment  granules,  instead  of  continuing  their  regular 
cycle  of  development  into  segmenting  forms,  are  transformed  into  the  young 
bodies  of  the  semi-lunar  phase.  This  transformation  takes  place  only  after 
a  number  of  febrile  paroxysms;  that  is  to  say,  only  after  the  parasite  has 
repeatedly  passed  through  its  regular  sporulating  cycle  of  development. 

The  young  bodies  of  the  crescentic  group  occupy  perhaps  one-quarter  of 
the  red  corpuscle.  Their  shape  is  round,  oval,  or  fusiform.  They  present 
a  characteristic  homogeneous,  refractive  appearance,  being  more  refractive 
than  the  presegmenting  bodies  with  central  blocks  of  pigment.  They  con- 
tain dark  pigment,  usually  in  the  shape  ef  fine  rods,  sometimes  collected  in 
a  mass,  but  oftencr  irregularly  distributed.  In  the  fusiform  bodies  the  pig- 
ment is  often  arranged  along  the  longitudinal  axis  of  the  spindle.  The 
haemoglobin  is  frequently  retracted  into  a  denser  stratum  around  the  bodies. 
These  bodies  increase  in  size  without  a  correspondingly  large  increase  in  the 
amount  of  pigment,  awd,  as  will  be  explained  later,  without  a  corresponding 
increase  in  their  chromatic  or  staining  substance — a  point  which  distin- 


508  MALARIA 

goiishes  the  direction  of  crescentic  development  from  that  of  the  regular 
sporulating  development. 

It  is  some  time  after  these  young  semilunar  bodies  have  begun  to  form  in 
the  bone  marrow  and  spleen  before  the  adult  crescents  appear  in  the  circulat- 
ino-  blood.  These  completely  developed  typical  crescents  are  on  the  average 
8-10  fi  long,  and  in  the  middle  2-3  /x  broad.  They  do  not  often  exceed  in 
length  one  and  a  quarter  or  one  and  a  half  times  the  diameter  of  a  red 
corpuscle.  They  present  a  characteristic,  homogeneous,  refractive  appear- 
ance. An  outer  double-contoured  border  can  sometimes  be  seen,  especially 
after  treatment  with  certain  reagents,  and  this  is  interpreted  by  Laveran, 
Mannaberg,  and  many  authors  as  evidence  of  a  distinct  enveloping  mem- 
brane ;  but  the  weight  of  evidence  is  opposed  to  the  view  that  the  crescents, 
any  more  than  any  other  form  of  the  malarial  parasite,  possess  a  membrane 
other  tlian  that  which  pertains  to  the  enveloping  red  corpuscle.  The  outer 
refractive  margin  of  the  crescents,  as  pointed  out  by  Antolisei  and  Angelini — 
who  interpret  it  as  a  cuticular  envelope  derived  from  the  red  blood  cor- 
puscle— may  be  slightly  colored  by  haemoglobin,  and  it  may  show  evidence 
of  this  presence  of  blood  coloring  matter  by  the  staining  with  eosin.  On  the 
typical  crescent  shaped  forms  a  fine  line  can  often  be  seen  stretching  like  a 
bow  across  the  concavity,  its  attachment  at  each  end  being  within  the  ex- 
tremities of  the  horns.  This  line  is  derived  from  the  red  blood  corpuscle 
within  which  the  crescent  has  developed,  and  represents  the  outer  contour 
of  the  partly  or  completely  decolorized  corpuscle.  This  contour  of  the 
corpuscle  can  sometimes  be  detected  also  on  the  convexity  of  the  crescent, 
and  parts  of  the  corpuscle  still  containing  haemoglobin  may  occasionally  be 
Been  on  the  margin  of  the  crescent,  or  the  whole  crescent  may  be  surrounded 
with  haemoglobin  containing  corpuscular  substance.  Similar  evidences  of 
the  partly  or  completely  decolorized  enveloping  blood  corpuscle  can  fre- 
quently be  seen  on  the  margin  of  the  round  and  oval  bodies. 

Bodies  of  the  crescentic  group  are  always  pigmented.  The  pigment  is 
very  dark  in  color,  often  black,  and  mostly  in  fine  rods.  In  the  typical  cres- 
cents the  pigment,  which  is  without  movement  and  in  fine  rods  and  grains, 
is  usually  collected  in  the  middle,  sometimes  in  a  single  clump  or  in  two 
clumps,  often  in  a  coronal  shape.  Mannaberg  emphasizes  the  frequency 
witli  wliich  the  pigment  is  arranged  in  two  adjacent  clumps  near  the  centre, 
presenting  a  figure-of-8  shape.  In  the  immature  crescents  the  pigment  is 
often  scattered,  or  is  arranged  longitudinally,  as  it  often  is  in  the  fusiform 
bodies.  The  amount  of  pigment  varies;  it  is  often  considerable.  In  certain 
pernicious  fevers  young  crescents  with  scattered  pigment  may  be  abundant 
in  the  blood.  In  tlie  oval  and  round  bodies  the  pigment  is  usually  con- 
centrated in  the  centre,  often  in  the  form  of  a  circle,  but  it  may  be  distributed 


MALAEIA  509 

throughout  the  bod3\  Ovoid,  round,  and  fusiform  bodies  may  be  changed 
into  typical  crescents,  and,  on  the  other  hand,  crescents  may  change  into 
fusiform,  oval,  and  round  bodies.  The  appearance  of  a  fusiform  or  ovoid 
body  may  be  presented  when  a  crescent  is  seen  from  the  convex  side. 

From  the  round  bodies  flagellate  forms  may  develop  in  the  manner  already 
described.  The  aestivo-autumnal  flagellate  bodies  develop  only  from  round 
bodies  of  the  crescentic  group.  They  are  smaller  than  the  tertian  flagellates, 
resembling  rather  the  quartan.  The  process  of  transformation  of  crescentic 
bodies  into  oval  and  round  forms,  and  the  development  of  flagella  from  the 
latter,  can  sometimes  be  observed  in  studying  the  fresh  blood  microscopically. 
Councilman  once  observed  a  rapid  undulatory  movement  of  a  body  present- 
ing the  general  appearance  of  a  crescent. 

Crescents  and  the  other  bodies  belonging  to  the  same  phase  not  infre- 
quently become  vacuolated  or  contain  or  throw  off  from  the  margin  little 
hyaline  balls  (pseudo-gemmation),  or  disintegrate  or  present  other  degen- 
erative changes.  Danilewsky  has  observed  crescents  of  unusually  large  size, 
as  much  as  20-22  /x  long  and  4-6  fi  broad. 

The  biological  significance  of  the  crescents  is  unknown.  These  bodies  do 
not  belong  to  the  regular  sporulating  cycle  of  development  of  the  parasite, 
and  there  is  no  positive  proof  of  their  capacity  for  further  development. 

Dr.  Thayer  in  a  personal  communication  to  the  writer  reports  a  valuable 
experiment  made  by  himself  which  demonstrates  the  incapacity  of  crescents 
when  inoculated  into  the  blood  of  healthy  individuals  to  develop  or  to  cause 
any  symptoms.  The  blood  was  taken  from  a  patient  who  had  had  acute 
aestivo-autumnal  fever,  which  was  arrested  by  administration  of  quinine. 
Crescents  persisted  in  the  blood.  For  seven  days  the  blood  was  examined 
without  finding  hyaline  bodies  or  any  form  of  the  malarial  parasite  other 
than  crescents.  Seven  days  after  the  disappearance  of  the  hyaline  bodies 
a  hypodermic  syringeful  of  blood  containing  crescents  in  considerable  num- 
ber was  withdrawn  from  the  median  basilic  vein  of  the  patient  and  imme- 
diately injected  into  the  corresponding  vein  of  a  healthy  man.  No  elevation 
of  temperature  or  other  symptoms  followed  the  injection,  nor  did  crescents 
or  any  parasitic  forms  make  their  appearance  in  the  blood,  which  was 
examined  daily  for  two  weeks  and  at  intervals  for  over  a  month.  In  the 
inoculation  experiments  of  Gualdi  and  Antolisei  and  others  in  which  it  is 
stated  that  the  blood  contained  only  crescents  and  infection  with  Haemd- 
tozoon  falciparum  followed  in  the  inoculated  individual,  it  is  probable  that 
hyaline  bodies  were  present  in  the  blood  used  for  the  inoculation  in  such 
small  number  that  they  escaped  detection. 

The  following  are  the  principal  views  which  have  been  advanced  regarding 
the  interpretation  of  the  crescents : 


510  MATERIA 

1.  Ijaveran  regards  the  crescentic  bodies  as  encysted  forms  from  which  the 
fla<''ella  develop.    There  is  no  proof  that  these  bodies  are  encysted, 

2.  Canalis  and  Antolisei  and  Angelini  believe  that  they  have  found  evi- 
dences of  sporulation  in  the  crescents  and  the  ovoid  and  round  bodies  be- 
longing to  the  crescentic  phase.  Grassi  and  Feletti  and  Sacharoff  likewise 
believe  that  these  bodies  may  sporulate.  Golgi  considers  them  capable  of 
reproductive  development  in  long  cycles,  and  brings  them  into  special  rela- 
tion with  relapses  and  with  fevers  of  long  intervals.  Most  observers  have 
been  unable  to  find  genuine  sporulation  or  other  evidences  of  reproduction 
in  these  bodies. 

3.  Grassi  and  Feletti  consider  that  the  crescents  belong  to  a  separate 
species  which  they  call  Laverania,  and  of  which  they  represent  a  regular 
phase  of  development.  The  sporulating  hyaline  bodies  with  which  the 
crescents  are  usually  associated  constitute,  according  to  these  writers,  dif- 
ferent species.  This  view  is  not  generally  accepted,  and  is  opposed  to  the 
observed  facts. 

4.  Mannaberg  regards  the  crescents  as  encysted  syzygies  formed  by  con- 
jugation of  two  aestivo-autumnal  parasites  and  capable  of  reproduction  by 
segmentation.  His  view  is  unconfirmed  by  any  other  observer,  and  is  im- 
probable. It  fails  to  explain  the  ovoid  and  round  bodies  which  belong  to 
the  same  phase  of  development,  and  it  cannot  be  reconciled  with  the  appear- 
ances noted  in  the  steps  of  development  of  the  crescents,  as  has  been  shown 
by  Bastianelli  and  Bignami. 

5.  Councilman  suggests  that  the  crescents  may  be  of  the  nature  of  spores. 
Several  authors  have  called  attention  to  a  resemblance  between  these  bodies 
and  the  falciform  spores  of  coccidia,  but  there  are  such  essential  differences 
between  the  two  that  the  apparent  resemblance  is  only  of  the  most  superficial 
character. 

6.  Bastianelli  and  Bignami  have  described  the  crescents  as  deviate  and 
sterile  forms.  This  has  been  interjireted  to  mean  that  they  regard  the  cres- 
cents as  degenerative  forms — a  view  held  by  Kruse  and  some  others — but 
in  their  latest  ])ul)litation  "  they  suggest  that  these  bodies  are  a  rudimentary 
]»hase  of  a  second  developmental  cycle  which  cannot  be  completed  within 
the  human  Wly,  but  requires  for  its  continuation  some  new  environments 
in  the  outer  world.  They  call  attention  to  the  occurrence  of  two  cycles  of 
development  in  several  unicellular  parasites,  especially  the  coccidia,  which, 
after  passing  through  several  generations  in  the  ordinary  parasitic  life, 
enter  upon  forms  belonging  to  a  second  cycle.     The  forms  of  this  second 

"Bastianelli  and  Bignami:  Studi  sulla  Infezione  Malarica.  Bullettino  della  R. 
Accademla  Medlca  dl  Roma.  Anno  XX,  1893-94. 


MALAEIA  511 

cycle  remain  sterile,  degenerate,  and  die,  unless  the  parasite  can  escape 
from  its  host  and  find  its  appropriate  new  conditions  of  life,  Manson  inde- 
pendently also  has  advanced  the  hyjiothesis  that  the  crescents  are  intended 
for  the  continuance  of  the  life  of  the  species  in  the  external  world.  It  has 
already  been  mentioned  that  a  similar  view  has  been  suggested  also  regard- 
ing the  significance  of  the  flagellate  bodies,  and  that  Manson  believes  that 
the  mosquito  may  serve  as  the  host  for  this  second  cycle  of  development. 

DIFFERENTIAL    DIAGNOSIS    OF    THE    VARIETIES    OF    THE    MALARIAL    PARASITE 

An  inexperienced  observer  may  possibly  mistake  for  the  unpigmented 
intracorpuscular  hyaline  forms  of  the  malarial  parasite  the  vacuoles  which 
occasionally  are  present  within  red  blood  corpuscles  or  the  clear  spots  which 
may  result  from  certain  deformities  in  the  shape  of  the  corpuscles.  These 
vacuoles  and  clear  spots  may  be  distinguished  in  the  fresh  specimen  by  their 
sharp  outlines,  the  absence  of  amoeboid  changes  of  shape  and  difference  in 
refraction  often  suggestive  of  an  empty  space  or  hole,  and  which  can  be 
described  less  readily  than  it  can  be  appreciated  by  actual  observation.  The 
absence  of  definite  staining  readily  distinguishes  these  vacuoles  from  the 
hyaline  bodies  of  the  parasite  in  stained  specimens. 

There  are  occasionally  seen  in  red  corpuscles  in  stained  specimens  of  the 
blood,  especially  in  anaemic  conditions,  small  stained  dots  which  do  not  bear 
much  resemblance  to  forms  of  the  malarial  parasite,  but  which  should  be 
known  to  the  observer  in  order  to  avoid  the  possibility  of  mistake.  They  are 
believed  by  some  to  be  the  result  of  degenerative  changes  in  the  corpuscles, 
and  by  others  to  be  remnants  of  nuclear  chromatin  derived  from  the  orig- 
inally nucleated  condition  of  the  red  corpuscle. 

Blood  plates  can  be  mistaken  only  for  free  spores  or  very  small  extra- 
corpuscular  hyaline  bodies.  In  general  no  attention  should  be  paid  as 
regards  diagnosis  to  bodies  free  in  the  plasma  which  resemble  blood  plates. 
In  fresh  specimens  it  is  practically  impossible  to  diagnose  free  spores  with 
any  certainty.  Clumps  of  blood  plates  have  been  mistaken  for  sporulating 
bodies,  but  they  can  be  readily  distinguished  from  the  latter  by  the  absence 
of  pigment. 

For  the  sake  of  convenience  the  principal  characters  which  enable  us 
to  distinguish  each  of  the  three  varieties  of  the  malarial  parasite,  and  which 
have  already  been  described  iii  detail,  will  here  be  summarized.  For  modi- 
fications and  amplification  of  these  general  statements  the  reader  must 
consult  the  detailed  descriptions  already  given. 

1.  Duration  of  the  Cycle  of  Development. — In  the  quartan  parasite, 
seventy-two  hours;  in  the  tertian,  forty-eight  hours;  in  the  aestivo-autum- 
nal,  irregular,  varying  from  twenty-four  hours  to  forty-eight  hours. 


612  MALARIA 

2.  Amoeboid  Hyaline  Bodies. — In  their  earliest  stages  often  indistin- 
guishable from  each  other.  Later,  those  of  the  quartan  parasite,  sharply 
outlined,  somewhat  refractive,  sluggishly  amoeboid,  with  development  of 
dark  brown  or  black,  relatively  coarse  pigment  granules,  which  have  but 
little  motion.  Amoeboid  movements  cease  in  a  relatively  early  stage  of 
development  of  the  pigmented  hyaline  body. 

Those  of  the  tertian  parasite,  pale  and  indistinct,  actively  amoeboid, 
with  development  of  reddish  brown,  actively  motile,  relatively  fine  pigment 
granules,  which  tend  to  accumulate  in  the  bulbous  swellings  at  the  extrem- 
ities of  the  delicate  branching  pseudopodia.  Amoeboid  movements  continue 
in  late  stages  of  development  of  the  pigmented  amoebae. 

Those  of  the  aestivo-autumnal  parasite,  small,  somewhat  refractive,  in 
repose  ring  shaped,  actively  amoeboid,  with  development  of  a  few  very  fine 
dark  reddish  brown  or  black,  only  slightly  motile,  pigment  granules,  ,or 
sometimes  without  pigment  throughout  all  phases  of  the  sporulating  cycle 
of  development. 

3.  Fully  Developed  Hyaline  Bodies. — Those  of  the  quartan  parasite  are 
somewhat  smaller  in  size  than  the  normal  red  blood  corpuscle,  and  are 
usually  surrounded  by  a  border  of  the  colored  refractive  substance  of  the 
enveloping  red  blood  corpuscle. 

Those  of  the  tertian  parasite  attain  the  full  size  of  a  normal  red  blood 
corpuscle  and  lie  in  swollen  decolorized,  red  blood  corpuscles.  Swollen, 
extracorpuscular,  transparent  bodies  with  dancing  pigment  granules  are 
common. 

Those  of  the  aestivo-autumnal  parasite  do  not  generally  exceed  one- 
quarter  to  one-third  the  size  of  the  red  blood  corpuscle.  The  enveloping 
corpuscle  is  often  shrunken  and  brassy.  They  contain  much  less  pigment 
than  the  quartan  and  tertian  forme,  and  sometimes  none  at  all. 

4.  Presegmenting  Bodies. — In  the  process  of  collection  of  the  pigment 
into  a  mass  or  block  in  the  centre  or  excentrically,  the  pigment  granules 
often  assume  a  more  regular  stellate  arrangement  in  the  quartan  than  in 
the  tertian  forms.  The  differential  points  between  the  three  varieties  in 
this  stage  relate  to  the  same  differences  in  size,  in  the  amount  of  pigment, 
and  in  the  condition  of  the  infected  corpuscles  as  have  been  mentioned 
under  the  preceding  heading.  The  presence  in  the  blood  of  quartan  and 
tertian  presegmenting  bodies  is  associated  with  that  of  sporulating  forms, 
whereas  with  the  aestivo-autumnal  presegmenting  bodies  sporulating  forms 
are  almost  always  missed  in  the  circulating  blood. 

5.  Sporulating  Bodies. — Those  of  tho  quartan  parasite  in  equal  propor- 
tion in  the  peripheral  and  the  splenic  blood.  They  are  somewliat  smaller 
than  in  the  red  corpuscles,  and  present  typical  rosette  forms  witli  a  division 


MALARIA  513 

into  six  to  twelve  ovoid  or  pyriform  segments,  each  segment  becoming  an 
oval  or  round  spore  containing  a  bright  nuclei  form  dot. 

Those  of  the  tertian  parasite  are  more  numerous  in  the  splenic  than  in 
the  peripheral  blood.  They  are  as  large  as  the  red  blood  corpuscle,  and 
present  less  regularity  in  segmentation  than  the  quartan  parasite.  They 
segment  usually  into  from  fourteen  to  twenty  spores,  which  are  a  little 
smaller  and  with  less  distinct  nucleiform  dot  than  those  of  the  quartan 
organism. 

Those  of  the  aestivo-autumnal  parasite  are  found  only  most  exceptionally 
in  the  circulating  blood  in  ordinary  cases.  They  are  abundant  in  certain  in- 
ternal organs,  including,  as  a  rule,  the  spleen.  They  do  not  generally  exceed 
one-third  to  one-half  the  size  of  the  red  blood  corpuscle.  They  segment  irreg- 
ularly, the  number  of  spores  being  sometimes  six  to  ten,  sometimes  ten  to 
twenty  or  even  more.  The  spores  are  smaller  than  those  of  the  quartan  and 
the  tertian  parasites.    The  stage  of  sporulation  is  a  prolonged  one. 

6.  Behavior  of  the  Infected  Corpuscles. — These  often  become  somewhat 
shrunken  and  deeper  in  color  in  the  quartan  infections ;  swollen  and  decolor- 
ized in  the  tertian;  and  shrunken  and  brassy,  sometimes  with  retraction 
of  haemoglobin  from  the  outer  part  of  the  corpuscle,  in  the  aestivo- 
autumnal. 

7.  Crescentic  Bodies. — Crescents  and  bodies  of  the  crescentic  phase  appear 
only  in  infections  with  the  aestivo-autumnal  parasite. 

8.  'Pigmented  Leucocytes. — Most  abundant  during  and  shortly  after  the 
paroxysm,  they  usually  disappear  during  the  period  of  apyrexia  in  quartan 
and  tertian  infections,  whereas  it  is  not  uncommon  to  find  them  in  all 
periods  of  aestivo-autumnal  infections. 

The  Intimate  Structure  of  the  Malarial  Parasite 

The  first  systematic  study  of  the  finer  structure  of  the  malarial  parasite 
was  made  by  Celli  and  Guamieri  (1888-89).  This  was  followed  by  similar 
investigations  by  Grassi  and  Feletti,  Eomanowsky,  Sacharoff,  Mannaberg, 
Antolisei,  and  Bastianelli  and  Bignami.  The  small  size  and  the  but  slightly 
differentiated  appearance  of  most  forms  of  the  parasite,  and  the  difficulty  of 
obtaining  clear  differential  stainings,  obscure  the  insight  into  their  intimate 
structure. 

Little  detail  of  structure  can  be  made  out  in  unstained  specimens.  The 
substance  of  the  parasite  presents  in  general  a  homogenous,  colorless,  hya- 
line appearance.  In  the  amoeboid  hyaline  bodies  of  the  quartan  and  tertian 
parasites,  particularly  in  the  larger  forms,  an  area  of  variable  size  in  the 
centre,  or  more  frequently  excentrically  placed,  may  sometimes  be  differ- 
entiated by  its  clear,  pale  appearance  from  the  more  refractive  outer  zone. 


514  MALARIA 

This  area  corresponds  to  the  unstained  struoture  interpreted  by  many- 
observers  as  the  nucleus  in  stained  specimens.  Occasionally  two  or  more 
such  clear  spaces  can  be  seen.  Sometimes  in  the  larger  amoeboid  and  the 
mature  forms  a  finely  granular  appearance  of  the  protoplasm  can  be  detected. 
It  is  particularly  characteristic  of  the  aestivo-autumnal  parasite  that  the 
young  intracorpuscular  hyaline  bodies  show,  when  at  rest,  a  clear  space 
surrounded  by  a  ring  of  protoplasm,  usually  thin  and  delicate  on  one  side 
and  thicker  on  the  other.  This  clear  space  appears  unstained  on  stained 
specimens.  The  mature  forms  in  which  the  pigment  has  collected  into  one 
or  more  clumps  appear  uniform  in  structure  in  fresh  specimens,  or  may  per- 
haps present  a  slightly  granular  appearance.  Within  the  spores,  especially 
distinctly  in  those  of  the  quartan  parasite,  a  bright  body  can  often  be  dis- 
tinguished, which  represents  the  nucleus  or  a  nucleiform  material. 

The  methods  for  staining  the  parasites  are  described  under  "  Diagnosis," 
(page  139,  Vol.  I,  "  Syst.  Pract.  M."  [Loomis],  1897).  These  methods 
are  useful,  not  only  for  the  study  of  the  finer  structure,  but  also  for  the  ready 
detection  of  the  unpigmented  young  hyaline  forms,  particularly  of  the 
aestivo-autumnal  parasites,  which  may,  without  very  careful  observation, 
escape  recognition  on  fresh  specimens,  whereas  the  presence  of  pigment  at 
once  attracts  attention  in  the  fresh  specimens  to  the  other  parasitic  forms. 

On  suitably  stained  specimens  the  intracorpuscular  young  hyaline  bodies 
show  a  stained  outer  part,  an  unstained,  usually  excentrically  placed,  in- 
ternal part,  and  one  or  more  deeply  stained  round  or  elongated  particles 
situated,  as  a  rule,  near  the  border  of  the  stained  and  unstained  parts.  The 
constant  unstained  part  is  not  to  be  confounded  with  vacuoles  which  may 
occasionally  be  present.  There  have  been  various  interpretations  of  the  struc- 
tures thus  differentiated.  Celli  and  Guarnieri  designated  the  stained  part  as 
ectoplasm  and  the  unstained  part  as  endoplasm.  The  deeply  staining  parti- 
cles they  interpreted  as  the  beginning  differentiation  of  a  nucleus,  which  they 
thought  they  could  recognize  in  larger  forms  as  a  definite,  stained  or  pale 
body  within  the  endoplasm,  Grassi  and  Feletti  do  not  recognize  a  division  of 
the  protoplasm  into  ectaplasm  and  endoplasm,  and  in  this  they  are  followed 
by  most  observers.  The  clear  unstained  part  they  interpret  as  a  relatively 
large,  vesicular  nucleus,  and  the  deeply  staining  particles  as  nucleoli  from 
which  may  proceed  a  delicate  reticulum  of  chromatin  connecting  them 
with  the  nuclear  membrane  which  they  assume  to  exist.  The  rest  of  the 
bladder-like  nucleus  is  filled  with  clear  nuclear  juice.  Although  not  all  of 
tliese  details  in  the  structure  of  the  nucleus,  such  as  the  membrane  and  the 
reticulum,  have  been  observed  by  subsequent  investigators,  Grassi  and 
Feletti's  interpretation  of  the  unstained  part  as  a  nucleus  and  of  the  deeply 
staining  particle  as  a  nucleolus  or  a  concentration  of  nuclear  chromatin  has 


MALARIA  515 

been  adopted  by  Celli  and  Sanfelice,  Romanowsky,  Sacharoff,  and  Manna- 
berg-,  and  has  been  widely  accepted. 

Bastianelli  and  Bignami,  while  not  denying  that  this  interpretation  is 
applicable  to  the  quartan  and  tertian  amoebae,  adopt  a  different  view  as  to 
the  structure  of  the  aestivo-autumnal  amoebae,  which  they  have  studied 
with  great  care.  They  differentiate  in  the  latter  an  outer  colored,  chromatic 
cytoplasm  in  the  form  of  a  stained  ring,  usually  thicker  on  one  side,  and  an 
inner  uncolored,  achromatic  cytoplasm,  which  is  all  of  the  clear  part  en- 
closed by  the  ring.  The  deeply  staining  chromatic  particle  they  find  in  the 
chromatic  and  not  in  the  achromatic  cytoplasm.  Often  there  are  two  par- 
ticles, each  at  opposite  points  in  the  ring.  This  particle  is  the  only  repre- 
sentative of  nuclear  material  in  the  parasite,  and  they  interpret  it  as  ful- 
filling the  functions  of  a  nucleus.  They  consider  that  the  rapidity  of 
development  and  multiplication  of  these  aestivo-autumnal  parasites  prevents 
the  formation  of  a  definite  nucleus  in  a  resting  stage,  such  as  is  described  for 
the  quartan  and  tertian  forms. 

According  to  Grassi  and  Feletti  and  Romanowsky,  the  nucleus  and  nu- 
cleolus can  be  found  in  all  stages  of  the  regular  cycle  of  development  of  the 
parasite.  The  nucleus  divides  directly — or,  according  to  Romanowsky,  by 
karyokinesis — to  form  multiple  nuclei  just  before  sporulation,  each  nucleus 
then  entering  into  the  structure  of  a  spore. 

The  evidence,  however,  is  in  favor  of  the  view  that  at  a  certain  stage  of 
development  the  nucleus  and  the  nucleolus  disappear  as  differentiated  struc- 
tures, the  latter  to  reappear  in  multiple  form  shortly  before  sporulation. 
Mannaberg  was  the  first  to  demonstrate  this  clearly  in  his  studies  of  the 
structure  of  the  tertian  parasite.  He  observed  that  as  the  amoebid  bodies 
approach  their  mature  form,  and  then  become  the  presegmenting  bodies, 
the  deeply  staining  particle  (nucleolus)  disappears,  and  later  the  clear, 
previously  unstained  part  (nucleus)  stains  diffusely,  so  that  there  is  in  this 
stage  no  definite  differentiation  of  structure  in  the  parasite,  although  the 
outer  part,  as  a  rule,  stains  more  deeply  than  the  central  part.  He,  however, 
speaks  of  the  outer  part,  which  contains  pigment  granules,  as  the  "  plasma 
part,"  and  the  inner  part,  into  which  the  pigment  does  not  penetrate,  as  the 
"  nuclear  part."  He  attributes  the  deeper  and  more  diffused  staining  of  the 
parasite  in  this  stage  to  the  solution  of  nuclear  chromatin  into  the  proto- 
plasm. The  first  evidence  of  sporulation  on  stained  specimens  is  furnished 
by  the  appearance  of  numerous  small,  deeply  staining  granules  of  chromatin 
in  the  periphery  of  the  protoplasm.  These  are  the  forming  nucleoli,  which 
increase  in  size  and  around  each  the  general  protoplasmic  substance,  during 
the  process  of  segmentation,  divides,  so  that  each  segment  or  spore  is  a  cell 
composed  of  a  nucleifonn,  deeply  staining  body  surrounded  by  its  pro- 


516  MALAEIA 

toplasmic  envelope.  In  the  quartan  and  tertian  spores  a  clear  unstained 
part  later  is  usually  differentiated  around  the  chromatin  granule,  and  the 
nucleus  now  resembles  that  seen  in  the  young  amoeboid  hyaline  bodies  with- 
in the  red  corpuscle. 

Bastianelli  and  Bignami  likewise  demonstrated  the  disappearance  of  the 
deeply  staining  nucleiform  body  in  the  forms  of  the  aestivo-autumnal  para- 
site containing  collected  pigment  (presegmenting  bodies),  and  soon  after- 
ward the  appearance  of  diffuse  staining  in  the  previously  achromatic  cyto- 
plasm, so  that  in  this  stage  no  sharp  differentiation  of  structure  can  be  made 
out  within  the  parasite,  which  is  richer  in  chromatic  material  than  before 
the  disappearance  of  the  nucleiform  body.  The  first  sign  of  sporulation  is 
the  formation  of  multiple  nucleiform  chromatin  granules  in  the  periphery 
and  the  development  of  spores  proceeds  in  the  manner  already  described, 
save  that  the  aestivo-autumnal  spores  are  composed  only  of  a  deeply  stain- 
ing nucleiform  body  immediately  surrounded  by  cytoplasm.  The  presence 
of  the  small,  clear,  unstained  part,  which  with  the  chromatin  particle  is 
interpreted  as  the  nucleus,  often  seen  in  the  tertian  and  quartan  spores,  is 
rarely  observed  in  the  aestivo-autumnal  spores. 

It  is  evident  from  this  description  Ihat  the  spores  of  the  malarial  parasite 
possess  a  definite  structure,  a  most  important  feature  being  the  presence  of 
a  deeply  staining  body  which  serves  the  function  of  a  nucleus.  The  recogni- 
tion of  this  structure  renders  it  possible  to  distinguish  from  genuine  spores 
the  various  pseudospores  which  have  been  at  times  erroaeously  interpreted 
as  phases  of  reproduction  of  the  parasite,  and  which  belong  to  the  category  of 
degenerative  forms.  Although  Antolisei  has  described  a  double  contour, 
which  he  interprets  as  a  membrane,  about  the  spores,  this  obsen^ation  has 
not  been  confirmed,  and  the  spores  are  to  be  regarded  as  naked,  thus  belong- 
ing to  the  class  of  gymnospores.  Some  have  objected  to  the  designation  of 
these  segments  as  spores,  but  this  nomenclature  is  in  accordance  with  that 
employed  by  zoologists  for  similar  bodies  formed  in  a  like  manner  in  certain 
other  unicellular  organisms. 

It  is  evident  from  the  preceding  description  that  investigators  are  not 
wholly  agreed  as  to  what  structure  in  the  malarial  parasite  shall  be  called 
the  nucleus,  some  applying  this  name  to  an  unstained  part  containing  the 
deeply  staining  chromatin  particle,  others  regarding  the  chromatin  granule 
itself  as  the  only  representative  of  the  nucleus.  There  is,  however,  general 
agreement  that  this  deeply  staining  particle  or  body  is  an  essential  constituent 
of  the  nucleus,  and  that  the  presence  of  a  nucleus  or  of  a  nucleiform  body  in 
the  parasite  has  been  demonstrated.  This  demonstration  fulfills  the  impor- 
tant biological  condition  that  something  performing  the  functions  of  a 
nucleus  belongs  to  every  cell  capable  of  reproduction,  and  it  has  served  to 


MALARIA  517 

remove  any  lingering  doubt  which  may  have  been  entertained  as  to  the  recog- 
nition of  these  bodies  as  parasitic  organisms 

It  is  interesting  to  note  that  during  the  regular  cycle  of  development  there 
is  a  continual  increase  in  the  amount  of  staining  or  chromatic  substance 
from  the  small  hyaline  body  to  the  sporulating  bodies,  and  that  the  cell 
becomes  multinucleated  just  before  segmentation  occurs.  As  the  chromatic 
substance  is  to  be  regarded  as  endowed  with  especial  functional  activity, 
these  changes  are  highly  significant. 

The  mature  crescents,  as  a  rule,  stain  feebly  and  diffusely,  or  often  only 
at  the  poles,  and  perhaps  also  along  the  margin.  Near  the  middle  one  or 
two  deeply  stained  granules,  often  covered  up  by  the  pigment,  may  be  present, 
but  they  are  not  constant.  Mannaberg  finds  often  a  narrow  stained  band  in 
which  are  two  or  more  deeply  stained  granules,  stretching  across  the  middle 
of  the  crescent.  Bastianelli  and  Bignami  find  that  the  young  developing 
bodies  of  the  crescentic  phase  stain  diffusely  and  less  intensely  than  the 
bodies  with  a  central  block  of  pigment  which  develop  into  segmenting  forms. 
Whereas  in  the  forms  of  the  parasite  which  develop  into  sporulating  bodies 
there  is  a  continual  increase  in  the  chromatic  substance  as  the  bodies  con- 
tinue to  develop,  in  the  development  of  the  semilunar  bodies  there  is  no 
correspondingly  large  increase  of  staining  substance.  With  rare  exceptions 
these  observers  found  no  chromatin  granules  in  these  developing  crescentic 
bodies,  nor  did  they  ever  find  in  any  body  of  this  group  those  changes  of 
structure,  such  as  the  appearance  of  several  chromatin  granules,  which  indi- 
cate sporulation, 

Laveran,  Celli  and  Guarnieri,  and,  with  especial  emphasis,  Mannaberg, 
consider  that  the  crescents  are  enveloped  in  a  double  contoured  membrane. 
A  number  of  other  observers  have  also  adopted  this  view.  We  do  not  con- 
sider that  any  definite  membrane,  which  can  be  regarded  as  a  part  of  the 
parasite  itself,  has  been  satisfactorily  demonstrated  around  the  crescents  or 
around  any  form  of  the  malarial  parasite.  A  double  contour  can  sometimes, 
but  not  regularly,  be  seen  in  the  periphery  of  the  crescents,  but  this  alone 
cannot  be  considered  as  proof  of  the  existence  of  a  membrane.  The  manner 
in  which  little  hyaline  pieces  (pseudo-gemmation)  can  sometimes  be  seen 
to  form  at  the  margin  of  the  crescentic  bodies  speaks  against  the  presence  of 
an  actual  membrane. 

THE  MALAEIAL  PIGMENT 

The  question  as  to  the  origin  of  the  malarial  pigment,  which  was  so  long 
discussed  without  conclusive  result  before  the  discovery  of  the  malarial 
parasite,  has  been  definitely  settled  by  this  discovery.  The  pigment  is 
formed  by  the  parasite  out  of  the  haemoglobin  of  the  blood  corpuscles  by 


518  MALARIA 

what  may  be  regarded  as  a  process  of  digestion.  The  pigment  occurs  in  the 
form  of  little  granules,  which  may  be  fine  or  coarse,  and  of  distinct  rods 
and  spicules,  which  may  be  as  much  as  1  /x  long.  Such  rods  often  present  a 
certain  superficial  resemblance  to  deeply  stained  bacilli.  The  pigment 
may  occur  in  the  form  of  extremely  fine  dust-like  particles  not  easy  to  detect. 
It  may  be  fused  into  black  blocks.  The  color  varies  from  a  yellowish  brown 
or  rusty,  reddish  brown  to  black,  Laveran  speaks  of  fire  red  and  even  light 
blue  pigment,  and  Rosenbach  observed  a  greenish  hue  of  the  pigment.  The 
malarial  pigment  is  somewhat  loosely  ranked  by  pathologists  among  the 
melanin  pigments.  The  differences  in  the  characters  of  the  pigment  be- 
longing to  the  different  varieties  of  the  malarial  parasite  have  already  been 
sufficiently  described.  The  deposition  of  the  pigment  in  the  various  organs 
wall  be  described  under  the  "  Pathological  Anatomy  "  (page  83,  Vol.  I, 
"  Syst.  Pract.  M."  [Loomis],  1898). 

Since  the  examinations  of  malarial  pigment  by  Meckel  and  by  Frerichs 
it  has  been  known  that  concentrated  sulphuric  acid  and  hydrochloric  acid 
do  not  alter  it,  and  that  it  disappears  upon  the  addition  of  strong  alkalies 
and  of  chloride  of  lime.  Kiener  observed  that  the  pigment  is  dissolved 
by  ammonium  sulphide. 

Tlie  demonstration  of  the  origin  of  the  malarial  pigment  from  the  blood 
coloring  matter  at  once  raised  the  question  whether,  like  many  pigments  of 
haematogenous  origin,  it  contains  iron  demonstrable  by  our  microchemical 
tests.  A  statement  by  Perls  as  long  ago  as  1867,  that  pigments  in  the  spleen 
of  intermittent  fever  respond  to  the  test  for  iron,  has  given  rise  to  much  con- 
fusion. It  is  not  wholly  clear  that  Perls  examined  the  malarial  pigment, 
but,  if  he  did,  there  can  be  no  doubt  that  he  mistook  for  the  true  malarial 
pigment  other  pigments  which  are  abundantly  present  in  certain  organs  of 
those  dead  of  malaria,  and  which  respond  to  the  chemical  tests  for  iro-n 
(haemosiderin).  It  has  been  sliowai  by  Neumann,  Bignami,  Stieda,  Dock, 
and  others  that  the  pigment  formed  directly  by  the  malarial  parasite  does 
not  contain  iron  in  a  combination  which  will  respond  to  our  ordinary  micro- 
chemical  tests  for  this  element.  This,  of  course,  does  not  prove  that  it  may 
not  contain  iron  in  some  combination,  such  as  that  in  haemoglobin,  which 
cannot  be  demonstrated  by  our  microchemical  reactions.  As  has  been 
pointed  out  by  the  writers  named,  the  organs  of  those  dead  of  malaria, 
j)articularly  the  spleen,  the  liver,  and  the  bone  marrow,  contain  a  large 
amount  of  haemosiderin,  the  presence  of  which  is  doubtless  to  be  explained 
by  the  extensive  destruction  of  red  blood  corpuscles  in  malaria.  There  is  no 
evidence  that  haemosiderin  is  formed  directly  by  the  malarial  parasite. 
Marchiafava  (1889),  however,  has  advanced  the  hypothesis  tliat  the  black 
pigment  may  be  formed  not  only  wifhin  the  malarial  parasites,  but  also 


MALARIA  519 

within  the  leucocytes  out  of  red  corpuscles  altered  by  the  action  of  the  para- 
site. He  thus  explains  the  intense  melanosis  of  the  spleen,  liver,  and  bone 
marrow  in  certain  aestivo-autumnal  pernicious  infections  where  the  para- 
sites appear  only  slightly  pigmented.  Bignami "  comes  also  to  the  conclu- 
sion, from  his  extensive  examinations  of  malanotic  organs  in  malaria,  that 
the  black  pigment  without  microchemical  iron  reaction  may  have  this 
double  origin,  being  formed  either  within  the  malarial  parasite  without  an 
intermediate  haemosiderin  stage  or  within  cells  out  of  haemosderin  derived 
from  destroyed  red  corpuscles.  The  objection  to  this  conclusion  of  Big- 
nami is  that  haemosiderin  is  found  in  the  liver,  spleen,  and  bone  marrow 
very  commonly  in  anaemias,  but  that  the  black  pigment,  without  micro- 
chemical  iron  reaction,  which  characterizes  malarial  infections,  does  not 
appear  under  these  conditions.  It  is  possible  that  the  malarial  parasite  may 
produce  some  chemical  change  in  the  substance  of  the  red  blood  corpuscle 
which  permits  the  transformation  of  the  specifieally  altered  haemoglobin 
into  black  malarial  pigment  within  certain  cells  of  the  body.  This,  how- 
ever, is  a  pure  hypothesis. 

PHAGOCYTISM 

The  presence  of  malarial  pigment  in  leucocytes  and  other  cells  has  long 
been  known.  Since  the  observation  of  phagocytic  phenomena  in  malaria  by 
Laveran,  Marchiafava  and  Celli,  and  Metchnikoff,  important  studies  of  this 
subject  have  been  made,  especially  by  Guamieri,  Golgi,  Bastianelli,  and 
Marchiafava  and  Bignami.^  These  investigations  have  shown  that  phaga- 
cytosis  is  a  common  and  important  phenomenon  in  malaria,  although  there  is 
much  difference  of  opinion  as  to  the  interpretation  of  some  of  the  observed 
facts.  Some  assign  to  the  phagocytes  no  higher  role  than  that  of  scavengers 
charged  with  the  collection  and  removal  of  the  pigment  and  debris  resulting 
from  the  activities  of  the  malarial  parasites  and  from  the  death  and  disin- 
tegration of  the  parasites  themselves.  The  amount  of  slag  which  is  produced 
in  severe  cases  of  malaria  in  the  form  of  pigment,  dead  and  disintegrating 
red  blood  corpuscles,  and  degenerated  and  broken  up  parasites  is  so  large 
that  even  this  office  of  scavengers  becomes  an  important  one.  But  Metchni- 
koff, Golgi,  and  some  others  believe  that  the  phagocytes  devour  large  num- 
bers of  intact,  healthy  parasites  in  certain  phases  of  their  development,  and 
that  in  this  contest  between  cell  and  parasite  is  to  be  found  the  most  im- 
portant agency  for  the  defence  of  the  body.    The  arguments  for  and  against 

^  BuUettino  della  Reale  Accademia  Medica  di  Roma,  Anno  XIX,  fasc.  II, 
p.  230,  1893. 

"  Especially  valuable  are  the  articles  of  Golgi,  II  fagocitismo  nell'  infezione 
malarica,  Riforma  Medica,  1888,  and  of  Bastianelli,  I  leucociti  nell'  infezione 
malarica.  Bull,  della  R.  Accademia  Medica  di  Roma,  1892. 


520  MALAEIA 

this  latter  conception  are  essentially  similar  to  those  which  are  adduced  as 
to  the  phagocytic  theory  in  bacterial  infections,  the  main  difficulty  being  to 
determine  to  what  extent  fully  active  and  virulent  parasites  are  taken  up 
and  destroyed  by  phagocytes,  and,  even  admitting  the  occurrence  of  this 
mode  of  disposal  of  the  parasites,  whether  or  not  it  is  the  most  essential 
and  the  predominant  factor  in  their  destruction.  That  malarial  parasites, 
as  well  as  bacteria,  may  perish  in  the  blood  plasma  without  incorporation 
within  cells  cannot  be  doubted,  as  we  have  direct  observations  demonstrat- 
ing this. 

The  cells  which  assume  the  functions  of  phagocytes  in  malaria  are  the 
leucocytes,  the  endothelial  cells  of  the  walls  of  the  blood  vessels,  and  large 
cells,  found  especially  in  the  spleen,  the  bone  marrow,  and  the  liver,  and 
called  by  Metchnikoff  "  macrophages."  Of  the  leucocytes  the  large  mononu- 
clear, the  polymorphonuclear,  and  the  transitional  forms  act  as  phagocytes. 
The  small  lymphocytes  and  the  eosinophils  have  never  been  observed  to  con- 
tain pigment  or  debris  in  malaria.  Of  the  leucocytes  it  is  the  large  mononu- 
clear forms  which  are  the  most  active  and  important  phagocytes  within  the 
body  in  malaria,  but,  as  has  been  pointed  out  by  Thayer  and  Hewetson,  the 
polymorphonuclear  leucocytes  are  the  ones  which  can  be  observed  to  be 
active  in  the  fresh  blood  during  examination  under  the  microscope.  It  is  the 
latter  which  pick  up  the  pigment  and  the  extracorpuscular  and  degenerated 
parasites,  and  which  attack  the  flagellated  bodies  in  the  fresh  blood  with- 
dravra  from  the  body,  so  that  there  may  be  a  notable  difference  between  the 
blood  examined  immediately  after  its  withdrawal  from  the  body  and  that 
examined  at  a  later  period  as  regards  the  number  of  polymorphonuclear 
leucocytes  containing  foreign  elements.  Endothelial  cells  containing  pig- 
ment, parasites,  or  fragments  of  parasites  or  of  red  corpuscles  are  rarely 
Been  in  the  circulating  blood  withdrawn  for  microscopical  examination ;  but 
the  study  of  microscopical  sections  of  organs  of  those  dead  of  malarial  in- 
fections shows  that  the  endothelial  cells  lining  the  capillaries  and  small 
blood  vessels,  especially  those  of  the  spleen,  bone  marrow,  and  liver,  in  cer- 
tain cases  also  of  the  brain,  intestine,  and  other  parts,  manifests  extensive 
phagocytic  activities.  So  too  the  macrophages,  although  they  have  repeatedly 
been  found  in  the  circulating  blood,  are  met  with  chiefly  in  the  splenic 
blood  and  in  the  microscopical  examination  of  organs  of  those  dead  of 
malaria.  These  macrophages,  which  may  attain  an  enormous  size  and  are 
frequently  destitute  of  nuclei,  and  therefore  necrotic,  are  mononuclear  cells 
derived  probably  in  part  from  mononuclear  leucocytes  and  certain  fixed 
cells  of  the  pulp  of  the  spleen  and  bone  marrow.  Their  contents  may  be 
varied,  consisting  sometimes  within  one  cell  of  pigment,  intact  or  degen- 
erated parasites,  and  red  blood  corpuscles  and  entire  smaller  phagocytes. 


MALAEIA  521 

Dock  has  counted  as  many  as  twenty  parasites  within  one  phagocyte  in  the 
spleen.  Under  "  Pathological  Anatomy  "  (page  83,  Vol.  I,  "  Syst.  Pract. 
M."  [Loomis],  1897),  will  be  described  the  appearances  of  these  various 
phagocytes  as  seen  in  sections  of  the  different  organs  of  the  body. 

Tlie  foreign  elements  which  are  found  within  these  phagocytes  in  malaria 
are — (1)  malarial  pigment;  (2)  yellowish  or  reddish-yellow  pigment  de- 
rived directly  from  disintegrated  red  corpuscles  (haemosiderin)  ;  (3)  red 
corpuscles,  sometimes  intact,  but  usually  more  or  less  altered  and  frag- 
mented; (4)  malarial  parasites,  either  free  or  enclosed  within  red  corpuscles, 
which  are  usually  altered,  such  parasites  appearing  sometimes  intact,  often 
degenerated  and  fragmented;  (5)  particles  which  are  probably  often  derived 
from  the  disintegration  of  parasites,  but  which  do  not  present  appearances 
sufficiently  characteristic  to  enable  one  to  determine  their  origin.  It  has 
already  been  mentioned  that  a  phagocyte  may  be  enclosed  by  a  macrophage. 
Leucocytes  either  with  or  without  pigment  may  be  thus  enclosed.  As  phago- 
cytes and  other  cells  often  degenerate  and  become  necrotic  and  disintegrated 
in  malaria,  it  is  evident  that  from  this  source  may  be  derived  material  for 
inclusion  within  living  cells. 

First  in  order  of  frequency  are  phagocytes  containing  malarial  pigment. 
In  the  examination  of  malarial  blood  obtained  from  the  peripheral  circula- 
tion the  only  form  of  phagocyte  which  is  to  be  seen  with  any  frequency  in 
the  perfectly  fresh  specimen  is  the  melaniferous  leucocyte.  Leucocytes  con- 
taining clearly  recognizable  parasites  are  rarely,  if  ever,  seen  in  the  freshly 
drawn  specimen  of  peripheral  blood.  Macrophages  containing  definite  para- 
sitic forms  may  occasionally  be  found  in  this  situation.  Both  mononuclear 
and  polymorphonuclear  leucocytes  may  contain  the  pigment,  but  in  the 
perfectly  fresh  specimen  the  former  preponderate.  The  pigment  is  found 
most  frequently  in  the  form  of  blocks  and  coarse  granules,  corresponding 
to  that  set  free  by  the  process  of  sporulation,  but  sometimes  the  pigment 
within  the  leucocytes  is  in  fine  rods  and  grains,  such  as  belong  to  the  earlier 
stages  of  development  of  the  parasite.  The  inference  is  a  probable  one  that 
in  the  latter  case  the  leucocyte  may  have  enclosed  the  parasite. 

As  has  already  been  stated,  in  the  fresh  blood  removed  from  the  body  and 
examined  for  a  while  under  the  microscope  the  polymorphonuclear  leuco- 
cytes can  be  seen  to  engulf  pigment  and  certain  parasitic  forms — viz.,  extra- 
corpuscular  forms,  especially  degenerated  and  fragmented  forms,  segmenting 
form  and  spores,  and  altered  red  corpuscles — and  especially  do  they  attack 
the  flagellate  bodies,  as  has  been  demonstrated  by  Thayer  and  Hewetson. 
Such  enclosed  parasitic  forms,  with  the  exception  of  the  spores,  can  be  seen 
rapidly  to  become  indistinct  and  unrecognizable  within  the  leucocytes. 
36 


522  MALAKIA 

From  the  examination  of  the  fresh  circulating  blood  alone  one  obtains  a 
very  inadequate  conception  of  the  extent  and  nature  of  the  phagocytic  proc- 
esses in  malaria.  A  fuller  idea  of  these  processes  can  be  derived  from  the 
study  of  blood  withdrawn  by  puncture  of  the  spleen,  where  phagocytic 
phenomena  are  far  more  active  than  in  the  circulating  blood;  but  it  is 
especially  in  the  microscopical  examination  of  the  organs  of  those  who  have 
puccimibed  to  a  malarial  attack  that  the  best  opportunity  is  offorded  to  learn 
the  extent  of  phagocytosis  in  malaria.  Here  one  finds  abundantly  leucocytes, 
endothelial  cells,  and  macrophages  containing  pigment,  parasitic  forms  and 
altered  red  blood  corpuscles. 

Parasites  in  their  later  stages  of  development,  especially  when  they  are 
free,  are  frequently  taken  up  by  phagocytes — in  their  early  stages  rarely, 
unless  tliey  have  become  extracorpuscular  or  the  corpuscle  containing  them 
is  degenerated.  Sporulating  forms,  and  somewhat  less  frequently  forms 
with  collected  pigment  (presegmenting  bodies),  are  the  ones  most  commonly 
found  in  a  recognizable  condition  within  the  phagocytes.  It  is  stated  by 
Bastianelli  and  Bignami  that  the  bodies  with  pigment  blocks  (presegment- 
ing) are  found  most  frequently  within  macrophages,  and  sporulating  forms 
within  polymorphonuclear  leucocytes.  Pigmented  amoebae  tliey  found 
rarely,  and  red  blood  corpuscles  containing  unpigmented  amoebae  very 
rarely,  within  phagocytes.  Bastianelli  gives  the  following  as  the  order  of 
frequency  in  which  the  various  parasitic  elements  are  found  within  phago- 
cytes: (1)  pigment;  (2)  sporulating  forms  and  spores;  (3)  red  corpuscles, 
normal  or  decolorized,  containing  sporulating  forms  or  bodies  with  central 
pigment  blocks;  (4)  brassy  and  decolorized  red  corpuscles  containing  Plas- 
modia (hyaline  bodies  in  the  amoeboid  stage)  ;  (5)  free  bodies  with  central 
j)igment  clumps;  (G)  more  rarely  free  amoebae  or  red  corpuscles  of  normal 
appearance  containing  parasites  in  the  amoeboid  stage.  According  to  the 
observations  of  the  writer,  free  bodies  with  central  pigment  clumps  occupy 
a  higher  place  in  this  scale  than  that  assigned  to  them  by  Bastianelli. 
Crescents  enclosed  in  phagocytes  may  be  found  even  in  the  circulating  blood. 
The  various  bodies  within  phagocytes  often  lie  in  an  area  surrounded  by  a 
clear  zone  like  a  vacuole. 

Golgi  (1887-88)  discovered  that  phagocytosis  occurs  in  quartan  and  ter- 
tian infections  with  a  definite  periodicity  which  stands  in  relation  to  certain 
phases  in  the  cyclical  development  of  the  parasite,  and  therefore  to  certain 
periods  of  malarial  fever.  This  is  readily  understood  when  one  considers 
that  it  is  especially  the  free  pigment  and  the  mature  and  segmenting  para- 
pi  tes  and  the  degenerative  forms  which  are  taken  up  by  phagocytes.  The 
pigment  is  liberated  by  the  process  of  sporulation  which,  as  has  already  been 
explained,  occurs  shortly  before  and  during  the  early  stages  of  the  paroxysm. 


MALARIA  523 

Corresponding  with  this,  Golgi  found  that  pigmented  leucocytes  are  present 
in  the  circulation  during  the  paroxysm  and  for  a  short  time  afterward,  and 
that  they  disappear  from  the  circulation  during  the  apyrexia.  This  perio- 
dicity in  the  appearance  of  melanif erous  leucocytes  and  of  other  phagocytes 
can  be  observed  regularly  in  quartan  and  tertian  infections.  There  are  fre- 
quently indications  of  it  also  in  aestivo-autumnal  infections,  but  on  account 
of  the  irregularities  in  the  cyclical  development  of  Haematozoon  falciparum, 
of  tlie  prolonged  period  of  sporulation,  of  the  frequent  occurrence  of  multiple 
groups  of  parasites,  and  of  the  presence  at  all  periods  of  degenerated  red 
corpuscles,  this  periodicity  in  the  occurrence  of  phagocytosis  is  often  ob- 
scured or  is  not  manifest  at  all.  Pigmented  leucocytes  may  be  found  in 
many  cases  of  aestivo-autumnal  infection  during  all  periods  of  the  disease, 
although  they  are  more  nuanerous  during  the  paroxysm  and  shortly  after- 
ward. In  the  severe  prolonged  cases  they  are  generally  abundant,  and  they 
may  persist  in  the  circulation  for  several  days  after  cure  is  effected.  As 
long  as  crescents  are  present  pigmented  leucocytes  may  be  found. 

Parasites  which,  to  all  appearances,  are  normal  are  found  within  phago- 
cytic cells.  What  is  the  fate  of  such  enclosed  parasites?  That  many  de- 
generate and  die  cannot  be  questioned,  for  these  degenerative  alterations 
can  be  directly  observed  in  progress  under  the  microscope  in  examining 
fresh  blood,  and  in  studying  malarial  blood  and  tissues  one  frequently  en- 
counters evidences  of  this  fate  of  the  parasites.  It  is  claimed,  however,  by 
Marchiafava,  Bignami  and  Bastianelli  that  enclosed  spores,  although  pre- 
vented from  further  development,  may  survive  for  a  long  time  within  leuco- 
cytes and  other  cells,  and  that  such  latent  spores  may  after  an  indefinite 
period  be  set  free  and  cause  by  their  development  a  relapse  of  the  fever. 

Attention  has  already  been  called  to  Golgi's  belief  that  the  aestivo- 
autumnal  parasite  may,  and  to  a  considerable  extent  does,  develop  within 
the  leucocytes  and  endothelial  cells  of  internal  organs,  in  ordinary  cases 
chiefly  of  the  spleen  and  bone  marrow.  He  adduces  a  number  of  considera- 
tions in  support  of  this  view,  but  the  objective  evidence  he  and  his  pupil, 
A.  Monti,  find  in  the  detection  of  the  frequent  presence  of  this  parasite, 
apparently  intact  and  in  all  stages  of  development,  within  these  cells.  In 
opposition  to  Golgi,  however,  it  is  claimed  by  Marchiafava,  Bignami  and 
Bastianelli  that  early  phases  of  development  of  the  parasite  are  rarely  seen 
within  the  cells,  and  that,  therefore,  the  much  more  commonly  enclosed  late 
phases  cannot  have  developed  within  the  cells  from  young  parasites.  Golgi 
also  brings  to  his  support  the  observation,  made  by  all  who  have  studied  the 
subject,  that  many  of  the  cells  containing  parasites  degenerate  and  die,  as  is 
made  evident  especially  by  the  loss  of  their  nuclei.  He  interprets  this  as 
meaning  that  in  the  conflict  between  cell  and  parasite  the  latter  often  comes 


524  MALARIA 

off  the  victor.  Further  investigations  are  needed  to  determine  to  what 
extent  Golgi's  doctrine  as  to  the  intercellular  residence  and  development  of 
Eaematozoon  falciparum  is  correct.  Certainly  the  greatly  preponderating 
number  of  intact  aestivo-autumnal  parasites  observed  in  examining  the 
organs  of  those  dead  of  pernicious  malaria  are  found  within  free  red  blood 
corpuscles  in  the  vessels  of  internal  organs. 

The  theory  of  Metchnikoff  that  the  essential  factor  in  the  resistance  of  the 
body  to  the  malarial  parasite  resides  in  the  activities  of  phagocytes  is  opposed 
by  many  considerations.  The  most  important  factors  in  determining  the 
gravity  and  the  course  of  a  malarial  infection  are  the  degree  and  quality  of 
virulence  possessed  by  the  parasite,  on  the  one  hand,  and  the  resistance  of 
the  individual  receiving  the  parasite,  on  the  other  hand.  There  is  no  evidence 
that  phagocytic  functions  are  in  abeyance  in  severe  and  pernicious  cases  of 
malaria.  On  the  contrary,  we  find  here  often  enormous  numbers  of  parasitic 
enclosures  within  phagocytes.  There  is  no  proof  that  spontaneous  recoveries 
from  malaria  are  associated  with  an  increase  of  phagocytic  activity.  Inas- 
much as  phagocytes  regularly  attack  degenerated  and  fragmented  parasites, 
and  as  we  know  that  such  degenerations  occur  frequently  within  parasites 
free  in  the  plasma,  it  is  permissible  to  suppose  that  many  of  the  parasitic 
forms  found  within  phagocytes  were  already  impaired  in  their  vitality  before 
they  were  engulfed  by  cells.  After  the  administration  of  quinine,  which 
directly  injures  the  malarial  parasite,  a  distinct  increase  in  the  number  of 
phagocytes  has  been  often  observed.  Certainly  quinine  does  not  stimulate 
the  leucocytes  to  swallow  the  parasites.  Here  the  increase  in  the  phagocytes 
must  be  attributed  to  the  increase  in  the  number  of  damaged  parasites. 

There  is  evidence  that  the  blood  plasma  may  exert  a  parasiticidal  effect 
upon  the  malarial  organism,  as  well  as  upon  other  protozoa  (Faggioli), 
when  the  parasite  has  escaped  from  the  protective  covering  of  the  red  blood 
coi-j)uscle.  The  period  when  the  largest  number  of  malarial  parasites  are 
destroyed  is  that  of  sporulation  and  of  free  spores,  and  it  is  during  this  phase 
of  the  life  history  of  the  parasite  that  quinine  acts  most  effectively.  We 
may,  at  least  provisionally,  adopt  a  theory  to  explain  natural  resistance  to 
the  malarial  parasite  similar  to  that  which  many  accept  regarding  resistance 
to  bacteria — viz.  that  the  parasites  are  destroyed  by  parasiticidal  substances 
contained  both  in  the  plasma  and  within  leucocytes  and  other  phagocytic 
cells.  The  substances  injurious  to  the  parasite  are  in  the  last  analysis  fur- 
nished to  the  plasma  by  the  cells,  and  are  in  a  more  concentrated  or  potent 
form  within  the  cells  than  in  the  fluids.  This  theory  assigns  to  the  phago- 
cytes a  higher  role  than  that  of  mere  scavengers.  They  are  endowed  in 
especial  degree  with  the  power  of  destroying  the  parasite,  but  this  power  is 
shared  by  the  plasma. 


MALAKIA  525 


PATHOGENESIS 


The  discovery  of  the  malarial  parasite  has  placed  within  our  reach  the 
means  of  solving  many  problems  concerning  malaria  which  we  could  not 
formerly  even  attack  with  any  hope  of  success.  Already  we  have  attained  a 
satisfactory  understanding  of  not  a  few  previously  unexplained  manifesta- 
tions of  malaria,  and  other  formerly  obscure  malarial  phenomena  have  been 
brought  at  least  within  the  range  of  our  comprehension.  Much  still  remains 
to  be  elucidated,  but  we  cannot  doubt  that  further  studies  will  continue  to 
throw  fresh  light  upon  what  remains  obscure. 

In  the  description  of  the  symptoms  and  lesions  of  malaria  attention  will 
frequently  be  called  to  their  relations  to  the  parasite,  and  in  this  connection 
only  certain  salient  points,  relating  more  particularly  to  pathogenic  proper- 
ties of  the  parasite,  require  consideration. 

The  mere  presence  of  the  malarial  parasite  in  the  body  is  not  sufficient  to 
cause  symptoms.  The  organisms  must  have  multiplied  to  a  certain  point 
before  their  presence  is  manifested  by  recognizable  symptoms.  The  bearing 
of  this  fact  upon  certain  malarial  phenomena,  more  particularly  upon  the 
varying  periods  of  incubation  as  determined  by  experimental  inoculations 
of  malarial  blood  and  upon  fevers  with  long  intervals,  will  be  considered  in 
the  clinical  part  of  this  article. 

It  may  be  stated  as  a  general  rule,  which  was  first  formulated  by  Golgi, 
that  the  larger  the  number  of  organisms  present  in  the  body  the  more  severe 
are  the  manifestations  of  the  disease;  but  the  number  of  the  organisms  is 
by  no  means  the  only  factor  which  determines  the  gravity  of  the  disease. 
The  variety  of  parasite  which  is  concerned  in  the  infection  is  a  factor  of 
fundamental  importance.  The  quartan  variety  produces  the  mildest  attacks, 
the  tertian  is  more  virulent  than  the  quartan,  and  the  aestivo-autumnal 
variety  is  the  most  virulent  of  all,  and  is  the  one  which  is  almost  exclusively 
associated  with  the  pernicious  attacks.  These  variations  in  virulence  are 
best  explained  upon  the  assumption  that  the  malarial  organism  produces 
toxic  substances  of  varying  virulence  according  to  the  variety  of  parasite. 
There  is  also  clinical  evidence  that  one  and  the  same  variety  may  vary  in 
virulence,  so  that,  for  example,  some  aestivo-autumnal  parasites  are  more 
virulent  than  others. 

In  seeking  an  explanation  of  the  varying  clinical  characters  of  malarial 
infections  we  have  to  reckon  not  only  with  the  number,  the  varieties,  and  the 
virulence  of  the  parasites,  but  also  with  several  other  factors,  such  as  pre- 
disposing conditions  on  the  part  of  the  individual  infected,  the  occurrence 
of  multiple  groups  of  the  parasite,  the  distribution  of  the  organisms  in  in- 
ternal parts,  the  circulatory  and  other  anatomical  disturbances  induced  by 
the  parasites. 


526  MALARIA 

Periodicity  is  the  most  striking  clinical  characteristic  of  malarial  fevers, 
and  the  explanation  of  this  phenomenon  lias  exercised  the  minds  of  pyretolo- 
gists  from  ancient  times.  It  is  true  that  intermittence  is  not  limited  to 
fevers  of  malarial  origin,  but  regularity  of  rhythm  in  the  occurrence  of 
the  paroxysms  is  especially  characteristic  of  malaria.  One  of  the  most 
interesting  additions  to  our  knowledge  resulting  from  the  discovery  of  the 
malarial  parasite  is  the  demonstration  by  Golgi,  which  has  been  abundantly 
confirmed,  that  this  rhythm  in  the  malarial  paroxysms  corresponds  to  a 
rhythm  in  the  development  of  successive  generations  of  the  parasite. 

The  onset  of  each  paroxysm  corresponds  to  the  ripening  and  sporulatioa 
of  a  generation  of  parasites  and  the  setting  free  of  a  new  brood."  Exactly 
what  the  connection  is  between  this  act  of  sporulation,  with  the  liberation 
of  a  fresh  brood  of  young  parasites,  and  the  cause  of  the  febrile  paroxysm, 
is  not  definitely  know^n.  It  was  at  first  suggested  by  Golgi  (1887)  that  the 
paroxysm  is  due  to  the  invasion  of  the  red  blood  corpuscles  by  the  new 
group  of  parasites,  but  it  was  shown  by  Antolisei  (1890)  that  the  paroxysm 
depends  rather  upon  the  act  of  segmentation  than  upon  the  invasion  of  the 
blood  corpuscles  by  a  new  generation  of  organisms,  for  quinine,  administered 
before  a  paroxysm  in  sufficient  quantity,  may,  by  destroying  the  fresh  brood, 
completely  prevent  the  invasion  of  the  red  corpuscles,  but  it  cannot  prevent 
the  segmentation  and  the  impending  paroxysm.  The  view  is  now  widely 
held,  and  seems  plausible,  that  in  the  act  of  sporulation  and  of  liberation 
of  the  spores  chemical  poisons  are  set  free,  and  that  these  poisons,  by  their 
action  on  the  nervous  centres  concerned  in  the  production  of  fever,  cause  the 

"  The  old  idea  that  the  periodicity  of  malarial  fevers  depends  upon  the  period- 
ical production  in  the  blood  of  a  materia  peccans  is  thus  confirmed.  It  is 
interesting  in  this  connection  to  note  the  line  of  argument  presented  by 
Griesinger  in  his  admirable  and  suggestive  article  on  the  malarial  diseases 
(Virchow's  Handb.  d.  spec.  Path.  u.  Therap.,  Bd.  II,  Abth.  2,  2te  Auflage,  p.  41, 
Erlangen,  1864) :  The  cause  of  the  periodicity  of  the  fever  cannot,  therefore,  be 
referred  to  the  disposition  of  the  nervous  system  to  rhythmical  vital  actions,  as 
many  have  formerly  done,  but  it  must,  at  least  according  to  our  present  although 
very  incomplete  knowledge  concerning  the  causes  of  heat,  be  attributed  to  some- 
thing periodically  occurring  in  the  blood,  which  is  connected  with  the  increased 
production  of  heat.  It  has  been  formerly  conceived  that  a  certain  substance,  a 
materia  peccans,  appears  periodically  in  the  blood  and  incites  the  febrile  heat 
and  reaction:  this  material  requires  for  its  production  and  complete  development 
sometimes  longer,  sometimes  shorter,  periods,  and  herein  lies  the  cause  of  the 
rhythm  of  the  fever As  an  explanatory  hypothesis  this  conception  accom- 
plishes   more    than    the    later    attempts    at    explanation The    continuous 

morbid  process  which  causes  the  poisoning  incites  periodically  changes  in  nutri- 
tion or  In  the  blood  which  arouse  the  nervous  apparatus  to  abnormal  manifes- 
tations. 


MALARIA  527 

febrile  paroxysms.  This  toxic  theory  of  malaria  has  been  elaborated  espe- 
cially by  Baccelli. 

The  fact  that  the  malarial  parasite  resides  in,  feeds  upon,  and  destroys 
the  red  blood  corpuscles  furnishes  an  entirely  satisfactory  explanation  of 
two  of  the  most  characteristic  and  important  manifestations  of  malaria — 
the  melanaemia  and  the  anaemia.  The  malarial  pigment,  for  which  we 
formerly  had  no  adequate  explanation,  is  formed  as  an  undigested  residue 
within  the  body  of  the  parasite  by  metabolic  processes  directly  out  of  the 
haemoglobin  of  the  infected  red  blood  corpuscle.  Various  stages  of  the 
formation  of  the  pigment  within  the  parasite  can  be  seen.  The  liberation 
of  this  pigment,  its  inclusion  by  phagocytes,  its  deposition  in  various  internal 
organs,  have  all  been  described,  and  will  be  further  considered  under  the 
"Pathological  Anatomy  "(page  83,  Vol.  I,  "  Syst.  Pract.  M."  [Loomis], 
1897).  The  relations  of  the  biological  characters  of  the  parasite  to  malarial 
anaemias  and  to  haemoglobinuria  will  be  fully  considered  in  the  anatomical 
and  clinical  parts  of  this  article  (pages  93,  116,  125,  and  130,  Vol.  I,  "  Syst. 
Pract.  M."  [Loomis],  1897). 

The  ways  in  which  the  red  blood  corpuscles  may  be  altered  by  the  action 
of  the  malarial  parasite  are  various.  The  extent  of  these  changes  varies 
with  the  variety  and  the  virulence  of  the  parasite.  They  are  least  in  quartan 
infections,  greatest  in  the  aestivo-autumnal.  The  infected  blood  corpuscle 
may  appear  otherwise  normal.  It  may  be  swollen  or  shrunken  or  variously 
deformed.  It  may  divide  into  two  or  more  pieces.  It  may  be  partly  or  com- 
pletely decolorized,  or  the  haemoglobin  may  separate  from  the  stroma  and 
be  dissolved  in  the  plasma,  or  may  be  concentrated  around  the  parasite. 
Especial  significance  in  the  aestivo-autumnal  infections  attaches  to  that 
alteration  in  the  corpuscle  which  has  been  repeatedly  referred  to  as  the  brassy 
change,  on  account  of  the  resemblance  in  the  color  of  the  shrunken  corpuscles 
to  brass,  sometimes  compared  also  to  copper  or  old  gold.  Nor  are  the  cor- 
puscles which  are  actually  infected  by  the  parasite  the  only  ones  which  may 
be  altered.  Uninfected  corpuscles  may  also  be  changed  in  appearance,  and 
may  be  destroyed,  especially  in  cases  of  haemoglobinuria. 

These  changes  in  the  red  blood  corpuscles,  which  must  be  regarded  as 
degenerative  and  destructive  cannot  be  brought  wholly  into  parallelism  with 
the  development  of  the  malarial  pigment.  In  fact,  the  most  profound  lesions 
and  the  greatest  destruction  of  the  red  corpuscles  occur  in  infections  with  the 
aestivo-autumnal  parasite,  which  is  characterized  by  the  small  amount  or 
even  the  entire  absence  of  pigment.  To  explain  many  of  these  changes  we 
must  have  recourse  again  to  the  theory  that  toxic  substances  are  produced 
by  the  parasite  and  directly  damage  the  blood  corpuscles. 


528  MALAEIA 

These  alterations  in  the  red  blood  corpuscles  not  only  explain  the  malarial 
anaemias  and  the  haemoglobinuria  with  their  concomitant  symptoms  and 
lesions,  and  the  accumulation  of  malarial  and  other  pigments  in  certain 
oro-ans,  but  they  are  utilized,  although  less  conclusively,  to  explain  certain 
other  malarial  phenomena.  We  know  from  physiological  observations  that 
the  physical  integrity  of  the  red  blood  corpuscles  is  an  important  condition 
in  the  maintenance  of  their  circulation  within  the  blood  current.  It  is 
reasonable  to  suppose  that  corpuscles  as  profoundly  altered  as  are  many  of 
those  infected  with  the  malarial  parasite  will  circulate  with  difficulty,  and 
will  tend  to  accumulate  in  certain  situations  where  local  conditions  of  the 
circulation  favor  the  lodgement  of  foreign  particles  which  get  into  the  circu- 
lation. Many  writers,  therefore,  attribute  to  these  alterations  in  the  physical 
properties  of  the  infected  red  blood  corpuscles  the  accumulation  of  the  para- 
sites within  the  vessels  of  certain  internal  organs,  more  particularly  the 
spleen,  the  bone  marrow,  the  liver,  and  the  brain,  and  they  explain  the  absence 
of  such  accumulation  in  quartan  infections  by  the  comparatively  slight  lesions 
of  the  infected  corpuscles,  and  the  large  accumulation  in  tertian,  and  still 
more  in  aestivo-autumnal,  infections  by  the  more  serious  damage  inflicted 
upon  the  infected  red  corpuscles  by  the  varieties  of  the  parasite  causing  these 
latter  infections.  Doubtless  these  factors — changes  in  the  infected  red  cor- 
puscles and  local  conditions  of  the  circulation — are  important  in  determining 
the  localization  of  the  parasites  in  certain  internal  parts,  but  with  our  present 
knowledge  we  cannot  explain  the  varying  distribution  of  the  parasites  ob- 
served in  different  cases  exclusively  by  their  aid,  any  more  than  we  can 
adopt  a  similar  explanation  for  the  localization  of  the  microorganisms  in 
other  infections. 

The  localization  of  the  parasites  in  some  cases,  more  particularly  in  aestivo- 
autumnal  infections,  within  definite  vascular  areas  of  internal  organs  stands 
in  relation  to  corresponding  symptoms  and  lesions.  The  comatose  and  the 
choleriform  types  of  pernicious  malaria  are  associated  with  an  accumulation, 
which  may  be  enormous,  of  the  parasites  in  the  capillaries  and  small  vessels 
of  the  brain  and  of  the  stomach  and  intestine  respectively.  Other  special 
localizations  of  the  parasites  will  be  mentioned  in  the  subsequent  part  of  this 
article.  In  these  cases  capillaries  and  other  small  bloodvessels  may  be  partly 
or  completely  plugged  with  parasites,  chiefly  within  red  blood  corpuscles. 
Swollen,  degenerated,  and  desquamated  endothelial  cells,  pigment,  macro- 
phages, and  other  phagocytes  contribute  to  this  occlusion  of  the  vessels. 
Genuine  thrombi  also  occur. 

Serious  disturbances  of  the  circulation  must  result  from  such  extensive 
plugging  of  the  vessels.  It  is  not  easy  to  determine  how  far  these  mechanical 
disturbances  of  the  circulation  are  responsible  for  symptoms  and  lesions 


MALARIA  529 

with  which  they  are  associated.  Marchiafava  and  Bignami  and  others  regard 
them  as  the  essential  cause  of  the  grave  nervous  symptoms  in  comatose 
pernicious  fever,  and  of  other  symptoms  and  of  lesions.  Many  years  ago 
Frerichs  likewise  attached  much  importance  in  the  causation  of  cerebral 
symptoms  to  accumulations  of  pigment  and  the  formation  of  coagula  within 
the  cerebral  vessels.  It  appears,  however,  to  the  writer  that,  aside  from 
certain  general  pathological  considerations  and  analogies  with  similar  con- 
ditions in  other  diseases,  this  mechanical  explanation  is  inadequate,  and  that 
here  too  the  toxic  products  of  the  parasite  are  operative.  The  promptness 
with  which  the  grave  cerebral  symptoms  may  subside  after  administration  of 
quinine  is  not  easily  reconcilable  with  the  theory  that  they  are  due  to  plug- 
ging of  the  vessels. 

Even  the  focal  necroses  which  are  common  in  the  liver  in  pernicious  cases, 
and  may  occur  in  the  spleen,  the  kidneys,  and  elsewhere,  are  best  interpreted 
as  due  to  the  toxic  products  of  the  parasite,  rather  than  as  the  result,  as  is 
claimed  for  the  liver  by  Guarnieri,  of  plugging  of  the  bloodvessels.  These 
necroses  do  not  differ  from  those  observed  in  diphtheria,  typhoid  fever,  and 
streptococcus  and  other  infections,  and  that  they  may  be  purely  toxic  in 
origin  has  been  demonstrated  by  Welch  and  Flexner."* 

The  capillary  hemorrhages  which  have  been  observed  in  the  brain  in  the 
comatose  form  of  pernicious  fever,  and  which  may  occur  elsewhere,  may  be 
referred  to  the  hyperaemia  and  stasis  resulting  from  plugging  of  the  vessels. 
The  interesting  fact  has  been  observed  that  in  these  capillary  haemorrhages 
the  extravasated  red  corpuscles  are  without  parasites,  while  the  neighboring 
bloodvessels  are  filled  with  red  corpuscles  containing  parasites.  The  ex- 
planation of  this  which  is  given  by  Marchiafava  and  Bignami  and  adopted  by 
others  is  that  the  corpuscles  containing  parasites  on  account  of  their  greater 
adhesiveness  stick  to  the  walls  of  the  vessels  and  thus  are  prevented  from 
escaping.  The  writer  offers  another  explanation  as  the  more  probable.  The 
examination  of  these  small  haemorrhages  shows  that  they  are  the  result  of 
diapedesis,  and  not  of  actual  rupture  of  the  vessels  (rhexis).  It  is  not  diffi- 
cult to  comprehend  that  red  corpuscles  altered  by  the  invasion  of  parasites 
would  not  participate  in  the  process  of  diapedesis,  whereas  it  is  not  easy  to 
understand  why  they  should  not  escape  from  ruptured  vessels. 

It  is  evident  from  what  has  been  said  that,  while  occlusion  of  vessels  and 
consequent  disturbances  of  the  circulation  are  common  in  severe  malarial 
affections,  and  are  doubtless  of  importance  in  causing  some  of  the  lesions 
and  symptoms,  the  more  important  and  characteristic  symptoms  and  lesions 
are,  in  the  opinion  of  the  writer,  with  our  present  knowledge,  better  explained 

^  The  Johns  Hopkins  Hospital  Bulletin,  March,  1892. 


530  MALARIA 

bv  the  toxic  tlieorj'  of  the  pathogenic  action  of  the  malarial  parasite  than  by 
any  mechanical  theories  which  have  yet  been  offered. 

We  have,  however,  no  positive  demonstration  of  the  existence  of  specific 
malarial  toxins.  The  investigations  as  to  the  toxicity  of  the  urine  of 
mahirial  patients  will  be  described  on  page  123  (Vol.  I,  "  Syst.  Pract.  IM." 
[Loomis],  1897).  They  have  not  led  to  any  positive  results  as  to  the  detec- 
tion of  specific  malarial  poisons. 

It  is  a  very  old  conception  that  the  febrile  reaction  of  the  malarial  par- 
oxysm is  conservative  in  the  sense  that  this  response  of  the  body  to  the 
presence  of  pyogenic  agents  in  some  way  aids  in  the  elimination  or  destruc- 
tion of  injurious  substances.  This  conception  is  not  altogether  without 
support  from  tlie  parasitological  study  of  malaria.  The  fever  begins  at  the 
time  of  the  birth  of  a  new  generation  of  parasites.  These  young  organisms 
before  they  have  entered  the  red  blood  corpuscles  are,  of  all  phases  of  develop- 
ment of  the  parasite,  in  the  most  vulnerable  condition,  as  has  been  shown 
by  investigations  of  the  action  of  quinine.  That  a  large  number  of  them 
perish  during  the  febrile  paroxysm  seems  to  be  demonstrated,  at  least  in 
quartan  and  tertian  infections,  by  the  contrast  between  the  number  of 
sporulating  forms  and  the  number  of  succeeding  infected  corpuscles.  Espe- 
cially suggestive  of  increased  potency  of  parasiticidal  agencies  during  the 
febrile  paroxysm  are  cases,  especially  of  quartan  or  tertian  infection,  in 
which,  after  a  sharp  paroxysm,  the  symptoms  and  the  parasites  disappear, 
perhaps  permanently,  but  often  to  return  after  a  long  interval  as  a  recrudes- 
cence of  the  fever  (page  121,  Vol.  I,  "  Syst.  Pract.  M."  [Loomis],  1897). 

SIMILAR  IIAEMATOZOA  IN  THE  LOWER  ANIMALS 

Great  interest  attaches  to  the  presence  in  the  blood  of  certain  lower 
animals  of  protozoan  parasites  closely  resembling  the  malarial  parasite. 
Attention  was  first  called  to  this  resemblance  ])y  Danilewsky  (1885-86), 
who  described  more  fully  certain  forms  which  were  previously  knovrn,  and 
added  the  discovery  of  new  forms,  especially  that  of  haematozoa  in  l)irds 
which  boar  close  resemblance  to  the  human  malarial  parasite.  Since  Dani- 
lewsky's  first  publications  there  have  been  a  number  of  investigations  on  this 
subject  by  Kruse,  Celli  and  Sanfelice,  Grassi  and  Feletti,  Laveran,  Labbe, 
and  others. 

In  the  blood  of  frogs,  turtles,  lizards,  and  some  other  cold-blooded  animals 
haematozoa  presenting  some  points  of  resemblance  to  the  malarial  parasite 
are  not  unconimon.  Of  these  the  best  studied  and  most  interesting  is 
Drepanidium  ranarum  (Lankcster),  identical  with  Gaule's  "Wurmchen," 
in  the  blood  of  frogs.  It  is,  however,  certain  haematozoa  in  birds  which 
bear  such  close  resemblance  to  the  malarial  parasite  that  their  identity  with 


MALARIA  531 

the  latter  has  been  assumed  by  Danilewsky  and  Grassi  and  Feletti,  who  speak 
of  the  existence  of  malaria  and  of  malarial  parasites  in  these  animals.  Most 
of  the  observations  thus  far  reported  have  come  from  Russia  and  Italy,  but 
the  parasites  have  been  found  in  birds  also  in  Germany  and  France,  and 
recently  in  the  United  States. 

In  birds  thus  infected  have  been  found  forms  similar  to  those  of  the 
malarial  parasite  in  man — viz.  unpigmented  and  pigmented  hyaline  bodies 
(which,  however,  in  distinction  from  similar  bodies  in  man,  manifest  little 
or  no  amoeboid  movement),  sporulating  forms,  crescents,  and  flagellated 
bodies.  The  bird's  haematozoa  are  also  parasites  of  the  red  blood  corpuscles, 
from  which  they  produce  black  pigment :  they  pass  through  the  same  stages 
of  development  as  the  latter,  and  the  same  diversity  of  views  exists  as  to  the 
origin  and  significance  of  the  crescents  and  flagellated  bodies.  The  name 
Haemoproteus  was  introduced  by  Kruse  to  designate  these  so-called  mala- 
rial parasites  of  birds,  and  various  other  names  have  also  been  suggested. 
Grassi  and  Feletti  adopt  the  same  names  and  the  same  classification  for  these 
parasite  of  birds  as  for  the  human  parasites  (page  487).  There  are  differ- 
ences between  the  haematozoa  found  in  different  species  of  birds,  and  in  the 
same  species  apparently  different  varieties  of  the  parasite  have  been  observed, 
but  there  are  at  present  no  definite  classification  and  no  certainty  as  to  the 
number  of  varieties  which  may  exist. 

Although  these  haematozoa  of  birds  evidently  belong  to  the  same  class  of 
organisms  as  the  malarial  parasite,  there  are  several  reasons  which  indicate 
that  they  are  not  identical  with  the  latter.  They  present  certain  morpho- 
logical and  physiological  differences  which  it  would  lead  too  far  here  to 
describe.  Although  found  thus  far  chiefly  in  birds  from  malarial  regions, 
it  is  not  proven  that  they  may  not  exist  in  birds  elsewhere.  The  inoculation 
of  uninfected  birds  with  the  blood  of  birds  containing  the  parasites  has  been, 
in  a  large  preponderance  of  the  experiments,  unsuccessful  in  the  result. 
The  inoculation  of  birds  with  blood  from  human  beings  affected  with  ma- 
laria, and  the  inoculation  of  human  beings  with  the  blood  of  birds  containing 
the  haematozoa,  have  been  uniformly  without  positive  result  (Di  Mattel). 
Large  doses  of  quinine  have  no  influence  upon  the  parasites  in  birds.  The 
presence  of  the  haematozoa  in  birds  is  usually  without  recognizable  disturb- 
ance of  the  health  of  the  birds,  although  it  may  cause  a  chronic  or  an  acute 
affection.  While,  then,  we  must  admit  a  close  relationship  between  certain 
haematozoa  of  birds  and  the  human  malarial  parasite,  the  existing  evidence 
is  opposed  to  their  identification. 


SO-CALLED  PAEASITIC  BODIES  IN  EPITHELIOMA* 

Under  the  microscope  are  specimens  of  carcinoma  which  show  various 
intracellular  formations  apparently  identical  with  some,  at  least,  of  the 
bodies  which  a  number  of  recent  observers  have  described  as  sporozoa  or 
similar  parasites.  There  are  also  sections  of  an  epithelioma  of  the  penis, 
made  from  pieces  which  had  been  placed  immediately  after  removal  in 
Fleming's  solution,  which  are  particularly  rich  in  these  intracellular  bodies. 
These  bodies  correspond  in  appearance  and  behavior  with  coloring  agents  to 
many  of  those  described  by  Sjobring  and  by  Siegenbeck  van  Heukelom. 
Most  of  them  appear  as  round  or  irregular  masses,  sharply  differentiated 
from  the  protoplasm  of  the  cancer  cell  enclosing  them  by  a  higher  refraction 
index  and  by  deeper  staining  with  eosin  and  safranin.  They  vary  in  size 
from  minute  globules  to  masses  which  occupy  the  greater  part  of  the  cell. 
They  occasionally  lie  in  a  vacuole  within  the  cell.  They  sometimes  contain 
one  or  more  particles  which  stain  deeply  with  haematoxylin.  Round  or 
irregular  particles,  staining  deeply  with  haematoxylin,  are  sometimes  found 
within  cancer  cells  presenting  normal  nuclei.  Some  of  the  inclosed  bodies 
are  pale  and  do  not  stain  deeply  with  any  of  the  dyes  employed,  but  are  more 
or  less  sharply  differentiated  from  the  surrounding  protoplasm.  These  pale 
bodies  are  usually  about  the  size  of  leucocytes,  or  somewhat  smaller,  and  fre- 
quently contain  nuclear  masses  resembling  fragmented  nuclei.  It  is  not  easy 
to  give  an  accurate  description  of  all  the  various  bodies  or  formations  which 
may  be  found  in  the  cells  of  an  epithelioma  more  or  less  sharply  differentiated 
from  the  surrounding  protoplasm. 

These  and  similar  enclosures  in  cancer  cells  must  be  familiar  to  all  who 
have  made  a  careful  study  of  epithelioma  and,  while  their  nature  cannot 
always  be  satisfactorily  determined,  it  is  entirely  premature  and  unwarranted, 
on  any  evidence  as  yet  brought  forward,  to  regard  them  as  sporozoa  of  other 
forma  of  parasites. 

Many  of  these  bodies  so  far  as  flat  celled  epithelioma  is  concerned,  can  be 
explained,  (1)  as  masses  of  keratine,  a  part  of  the  protoplasm  having  under- 
gone in  a  circumscribed  area  the  keratine  metamorphosis,  while  the  rest 
remain  granular;  (2)  as  irregular  masses  of  eleidin  or  kerato-hyalin;  (3)  as 

» Report  of  remarks  before  the  Johns  Hopkins  Hospital  Medical  Society,  Balti- 
more. October  6,  1S90. 

Johns  Hopkins  Hosp.  Bull.,  Bait.,  1889-90,  I,  97-98. 

532 


PARASITIC  BODIES  IN  EPITHELIOMA  533 

included  leucocytes  undergoing  degenerative  changes,  with  or  without  frag- 
mentation of  nuclei;  (4)  as  scattered  nuclear  fragments  derived  from  the 
preceding. 

-  Just  as  epithelioma  is  essentially  an  atypical  growth  of  epithelium,  so  it 
is  not  surprising  to  find  various  atypical  metamorphoses  of  the  epithelial 
cells,  such  as  partial  transformation  of  the  cell  protoplasm  into  kerato-hyaline 
and  into  keratine. 


THE  PARASITE  OF  CANCER' 

"Dr.  Oaylord  has  hrought  before  us  something  more  than  the  mere  descrip- 
tion of  the  so-called  cell  enclosures  observed  in  hardened  specimens  of  cancer. 
Of  the  enclosures  hitherto  described  in  preserved  material  the  only  ones 
which  present  anything  like  a  definite  organization  and  which,  it  seems  to  me, 
have  not  been  altogether  satisfactorily  explained  are  the  bodies  first  accu- 
rately described  by  Thoma  and  Sjobring,  and  subsequently  noted  by  most 
of  those  who  have  studied  the  subject.  These  bodies  in  English  and  Amer- 
ican writings  are  often  designated  without  much  propriety  as  "  Plimmer's 
bodies."  No  conclusive  evidence  that  these  bodies,  still  less  that  any  other 
of  the  various  enclosures,  are  parasites,  has  been  furnished,  and  it  now 
seems  evident  that  no  further  progress  in  the  search  for  parasites  is  likely 
to  be  made  by  the  examination  of  hardened  material  with  our  present 
methods. 

Under  these  circumstances  it  is  important  to  turn  to  the  examination  of 
fresh  material  and  to  make  attempts  to  cultivate  parasitic  organisms,  pro- 
vided such  exist  in  cancer  and  other  malignant  tumors.  This  direction  of 
study  has  therefore  been  followed  in  recent  years  by  several  investigators, 
and  it  is  especially  his  results  along  these  lines  which  Dr.  Gaylord  has  re- 
ported. As  regards  artificial  cultures,  it  is  certain  that  no  forms  of  bacteria 
demonstrable  by  existing  methods  are  directly  concerned  in  the  causation 
of  cancer,  and,  notwithstanding  the  stronger  claims  made  in  behalf  of 
Blastomycetes,  I  am  glad  to  learn  that  Dr.  Gaylord  rejects  these  claims  and 
takes  a  position  in  this  regard  opposed  to  that  of  Sanfelice,  Roncali, 
Plimmer,  Leopold,  and  others.  He  interprets  as  protozoa  the  bodies  which 
he  regards  as  parasites. 

I>'aving  out  of  consideration  the  occasional  and  accidental  presents  of 
cultivable  bacteria  and  yeasts  in  cancer,  I  question  whether  what  is  called 
by  Dr.  (Jaylord  and  other  investigators  as  the  cultivation  of  protozoa  or  of 
eporozoa  from  cancers  should  be  so  designated,  and  it  does  not  appear  that 
Becondary  cultures  carried  on  from  generation  to  generation  have  in  any 
instance  been  secured. 

'  Remarks  on  a  paper  entitled.  The  Parasite  of  Cancer  with  Demonstrations, 
by  Harvey  R.  Gaylord.  before  the  Johns  Hopkins  Hospital  Medical  Society, 
Baltimore.  April  15.  1901. 

Johns  Hopkins  Hosp.  Bull.,  Bait..  1901.  XH,  295-296. 

534 


PARASITE  OF  CANCER  535 

There  is  not  much  agreement  among  different  observers  either  in  the 
description  or  the  interpretation  of  the  various  bodies  regarded  by  them  as 
parasites  to  be  seen  in  fresh  cancerous  material  or  fluids,  or  in  such  material 
kept  free  from  bacterial  contamination,  whether  mixed  with  some  cultural 
fluid  or  not.  Dr.  Gaylord  lays  especial  emphasis  upon  the  presence  in  can- 
cers and  other  conditions  of  homogeneous,  yellowish,  spherical  bodies  re- 
sembling droplets  of  fat  but  without  the  usual  reactions  for  fat,  and  he 
considers  that  he  finds  evidences  of  multiplication  of  these  bodies  and  of  their 
passing  through  a  definite  cycle  of  development  which  he  describes.  He  is, 
I  trust,  prepared  for  a  considerable  degree  of  skepticism  following  this 
announcement  of  his  results,  and  it  is  desirable  that  this  should  be  the  atti- 
tude of  mind  until  we  are  in  possession  of  more  evidence  than  has  as  yet 
been  furnished  in  favor  of  the  parasitic  hypothesis.  It  is,  however,  incum- 
bent upon  pathologists  to  make  a  careful  study  of  all  that  can  be  seen  in 
the  microscopic  examination  of  fresh,  macerated,  and  preserved  cancerous 
material,  and  whatever  else  may  be  the  outcome  of  such  studies,  they  will 
have  furthered  our  knowledge  of  cellular  degenerations  and  metamorphoses. 
Unless  there  are  those  present  who  on  the  basis  of  such  study  are  prepared  to 
discuss  Dr.  Gaylord's  findings,  it  does  not  seem  to  me  worth  while  to  discuss 
them  in  detail. 

Dr.  Gaylord  has  presented  an  instance  of  multiple  nodules  in  the  lungs 
of  an  adenocarcinomatous  nature  following  the  intravenous  injection  of 
cancerous  ascitic  fluid.  With  this  exception  and  one  or  two  more  doubtful 
cases  his  experimental  results,  so  far  as  the  reproduction  of  malignant 
tumors  is  concerned,  are,  like  those  of  other  investigators  in  the  same  line, 
negative. 


EXHIBITION  OF  ANIMAL  PAEASITES' 

These  parasites  were  collected  from  domestic  animals  in  Baltimore,  during 
the  previous  two  years  as  opportunity  offered,  no  attempt  being  made  to 
have  the  collection  complete.  The  interest  in  animal  parasites  has  been 
overshadowed  of  late  years  by  the  study  of  the  pathogenic  bacteria,  but 
nevertheless  the  entozoa  are  of  great  interest  and  importance  and  deserve 
our  careful  attention. 

1.  From  the  horse: 

Spiroptera  megastoma  (or  Filaria  megastoma) .  The  stomachs  show  the 
honey-combed  submucous  tumors,  with  ulcerated  mucosa,  containing  the 
large-mouthed  maw-worms.  This  parasite  is  not  very  rare  in  the  horses  of 
this  region,  but  in  none  of  the  cases  in  which  it  was  found,  was  there  evi- 
dence that  it  had  materially  damaged  the  usefulness  of  the  animal. 

Strongylus  armaius.  Here  are  several  specimens,  gross  and  microscopical, 
of  verminous  aneurism  of  the  anterior  mesenteric  artery.  The  presence 
of  the  palisade  worms  in  the  bloodvessels  causes  interesting  histological 
changes.  This  parasite  with  the  resulting  aneurisms  is  common  in  horses 
of  this  region.    In  one  instance  it  had  caused  fatal  colic. 

Gastrophilus  equi.  Here  is  a  stomach,  the  mucous  membrane  of  which 
near  the  cardia  is  completely  covered  with  bots. 

2.  From  the  cow : 

Actinomyces  bovis.  Although  this  is  a  vegetable  parasite,  the  opportunity 
is  taken  to  show  a  number  of  specimens  of  actinomycotic  tumors  from  the 
jaws  and  other  parts  of  the  cow.  On  account  of  the  absence  of  any  satisfac- 
tory laws  regulating  the  inspection  of  meat  in  this  state,  the  number  of 
cattle  affected  with  actinomyces  brought  to  Baltimore  and  slaughtered  here 
for  the  market  is  unusually  large  and  there  is  rarely  any  difficulty  in  pro- 
curing specimens  of  this  disease.  Attempts  have  been  made  to  cultivate  the 
organisms  according  to  the  directions  given  by  Bostrom  but  without  success. 
No  instance  in  which  the  actinomyces  has  been  found  in  human  beings  has 
been  recorded. 

Cystircrcus  taeniae  mediocanellatae.  This  parasite  was  found  once  in  the 
heart-muscle  of  a  cow. 

Strongylm  jnicniriis.  A  number  of  cases  of  verminous  bronchitis  and 
pneumonia  in  calves  due  to  this  parasite  have  been  observed  and  here  are 
microscopical  sections  of  the  lungs  so  affected. 

Filiana  labia to-papillosa  (Alessandrini).  This  worm  was  found  free  on 
the  peritoneal  surface  of  a  cow  without  causing  any  apparent  injury. 

•  Report  of  remarks  before  the  Johns  Hopkins  Hospital  Medical  Society,  Balti- 
more, March  17,  1890. 

Johns  Hopkins  Hosp.  Bull.,  Bait.,  1890,  I,  72-73. 

53R 


EXHIBITION  OF  ANIMAL  PARASITES  537 

3.  From  the  sheep : 

Taenia  expansa.  This  parasite  was  found  in  the  small  intestine.  It  is 
quite  common. 

Strongylus  contortus.  The  parasite  was  found  in  large  numbers  in  the 
stomach  of  several  sheep  which  had  died  at  Druid  Hill  Park  without  other 
apparent  cause  of  death. 

4.  From  the  hog : 

Echinococcus.  Echinococci  were  found  in  several  hogs  which  had  been 
born  and  reared  in  the  neighborhood  of  Baltimore,  but  this  parasite  is  not 
common  in  this  region.  Sections  of  the  liver  are  shown  illustrating  every 
stage  of  development  of  this  l)ladder  worm  from  cysts  smaller  than  a  pea  up 
to  cysts  as  large  as  an  orange.  Here  are  specimens  of  the  taenia  echinococ- 
cus produced  by  feeding  the  cystic  worms  to  a  dog. 

Cysticercus  cellulosae.  The  pork  measles  has  been  found  in  only  a  few 
instances. 

Echinarhynchus  gigas.  This  worm  is  common  in  the  swine  of  this  region 
and  appears  to  be  common  throughout  the  United  States.  The  ulcerated 
and  necrotic  patches  in  the  inner  wall  of  the  small  intestine  caused  by  the 
attachment  of  tlie  thorn-headed  worm,  bear  some  resemblance  to  the  necrotic 
foci  resulting  from  hog  cholera.  In  only  one  instance  had  the  gut  been 
actually  perforated  by  this  worm, 

Trico-cephalus  crenatus.    This  parasite  was  very  common  in  the  caecum. 

Ascaris  suilla,  believed  by  many  to  be  identical  with  Ascaris  lumbri- 
coides.  It  was  not  very  often  met  with.  In  one  case  the  small  intestine  for 
a  distance  of  40  cm.  was  found  packed  full  of  ascarides,  but  there  were  no 
evidences  of  intestinal  obstruction  and  it  is  questionable  whether  this  accu- 
mulation of  the  worms,  so  as  apparently  to  obstruct  the  gut,  is  not  a  post- 
mortem occurrence, 

Sclerostoma  pinguicola  (Verrill),  believed  to  be  identical  with  Stephan- 
urus  denatus  (Diesing),  although  this  identity  is  not  absolutely  certain. 
This  interesting  worm  was  found  in  the  abdominal  adipose  tissue  and  in  the 
liver.  The  presence  and  mode  of  migration  of  this  parasite  in  the  liver  of 
swine  have  not  hitherto  been  described.  Sclerostoma  pinguicola  was  found 
in  the  livers  of  eleven  swine,  and,  while  not  very  frequent,  cannot  be  con- 
sidered a  rarity  in  this  situation.  It  is  found,  often  in  large  numbers, 
in  the  main  trunk  and  branches  of  the  portal  vein,  which  then  usually  con- 
tain parietal  or  occluding  thrombi  in  which  the  worms  are  imbedded.  The 
real  habitat  of  the  worm  is,  however  the  connective  tissue  around  the  portal 
vessels.  In  this  tissue  it  burrows  its  way,  producing  inflammatory  masses 
of  new  connective  tissue  rich  in  leucocytes.  On  section  of  the  liver,  nodules 
and  bands  with  sinous  cavities  containing  a  brownish  or  reddish  white  puru- 
lent fluid  are  observed.  Similar  nodules  are  also  visible  projecting  on  the 
surface  of  the  liver.  In  these  sinous  cavities  the  parasite  may  be  found,  or 
it  may  be  absent,  having  made  its  way  to  other  parts.  The  worm  finds  its 
way  into  the  portal  vessels  by  ulceration  from  the  peri-portal  tissues  through 
the  walls  of  the  vessels,  and  in  several  instances  the  worm  could  be  demon- 
strated partly  without  the  vein.  Before  actual  penetration  into  the  vein 
there  occurs  a  bulging  inward  of  the  vessel  wall  on  which  forms  a  thrombus 
composed  primarily  of  blood  platelets.  One  of  the  most  interesting  his- 
37 


538  EXHIBITION  OF  ANIMAL  PARASITES 

tolocrical  chansres  produced  bv  the  inva^^ion  of  this  parasite  into  the  liver  is 
an  t^xtensive  new  growth  of  the  mucous  glands  in  the  walls  of  the  bile  ducts. 
This  new  growtii  occurs  in  tlie  areas  of  newly  formed  connective  tissue  in 
the  nei'diborhood  of  the  parasites.  Actual  adenomatous  formations  of  un- 
doubted parasitic  origin  are  produced  in  this  way.  The  same  alteration  has 
been  recently  described  and  pictured  by  Schaper  in  connection  with  disto- 
niatosis  of  the  liver  ("Deutsche  Zeitschrift  fiir  Thiermedicin/'  Bd.  VI, 
p.  1).  On  section  of  the  worms,  as  found  in  the  liver,  leucocytes  with  well 
stained  nuclei,  resembling  those  in  the  fluid  of  the  cavities  containing  the 
wornii5,  can  Ix^  seen  in  the  intestinal  canal  of  the  worm,  but  whether  this  can 
be  interpreted  as  evidence  that  the  pus  cells  produced  by  the  presence  of  the 
worm  actually  serve  as  its  food  is  uncertain.  Sometimes  the  lesions  of  the 
liver,  which  have  been  described  were  extensive,  the  surface  and  interior  of 
the  organ  presenting  a  large  number  of  ])arasitic  foci,  and  it  would  seem  as 
if  such  an  extent  of  the  disease  must  be  injurious  but  no  cases  were  observed 
in  which  the  death  of  the  animal  could  be  attributed  to  the  presence  of 
Sclerosloma  pinguicoJa.  The  parasite  as  found  in  the  liver  and  as  found  in 
the  well  known  foci  in  the  al)doniinal  fat  tissue  is  identical.  Here'are  instan- 
ces in  which  the  main  trunk  of  the  portal  vein  as  it  enters  the  liver  is  com- 
pletely occluded  by  a  thrombus  containing  the  sclerostomata. 

StroHfjijlus  paradoxus.  This  strong}'le  is  extremely  frequent  in  the  bron- 
chi of  the  swine  in  this  region.  Its  presence  was  found  to  be  the  direct 
cause  of  death  in  three  pigs.  In  these  cases  the  trachea  and  bronchi  con- 
tained aji  almost  incredible  number  of  strong}'les,  so  that  on  sections  of 
the  lung,  tlie  medium-sized  and  small  bronchi  appeared  filled  with  worms. 
Strongi/lm  jiaradoxm  is  usually  associated  with  some  bronchitis  and  often 
with  broncho-pneumonia,  but  it  may  be  present,  even  in  large  numbers, 
without  eitlier  bronchitis  or  pneumonia.  In  fact  in  one  of  the  fatal  cases 
in  which  the  strongyles  appeared  to  fill  the  medium-sized  and  small  bronchi 
and  were  present  in  enormous  numbers  in  the  trachea  and  large  bronchi 
there  was  no  trace  of  pneumonia  and  scarcely  any  bronchitis.  The  animals 
suffered  from  extreme  dyspnoea  and  the  heart  pulsated  so  violently  as  to  be 
visible  at  a  distance  and  to  communicate  it*  motion  to  the  entire  thorax.  At 
the  aut(>i)sy  the  right  ventricle  was  hypertrophied.  The  favorite  habitat  of 
the  worms  when  present  only  in  moderate  number  is  in  the  bronclii  in  the  pos- 
terior part  of  the  caudal  lolx>s,  and  sometimes  their  numlK^r  is  so  small  that 
cronsiderable  searching  is  required  to  detect  them.  There  is  usually  a  little 
niuco-pus  in  the  thrombi  where  the  strongyles  are  lodged  even  when  there  is 
no  general  bronchitis.  The  adjacent  lung  parenchyma  is  often  emphysem- 
atous or  on  the  other  hand  it  may  be  simply  atelectatic  or  it  may  be  the  seat 
of  a  broncho-pneumonia.  Frequently  there  is  a  broncho-pneumonia  of  the 
ventral  lobes  when  the  worms  are  to  l)e  found  only  in  the  posterior  ])arts  of 
the  cAudal  lobes.  The  broncho-pneumonia  associated  with  Sfrongi/Jus  pnra- 
(loTUJi  appears  as  a  browniish  or  grayish  red  consolidation  in  which  the 
individual  lobules  and  lobulettes  can  be  felt  and  seen  as  nodules.  The 
affected  part  is  not  much  swollen  and  there  is  generally  no  pleuritic  exuda- 
tion. On  microscopical  section  the  air  cells  contain  leucocytes,  e])ithelioid 
cells,  sometimes  fibrin  and  red  blood  corpuscles  and  frequently  ova  of  the 
Ktrongylcs.    These  ova  are  often  partly  or  completely  enclosed  within  giant 


EXHIBITION  OF  ANIMAL  PAKASITES  539 

colls  By  a  combination  of  Weigert's  fibrin  stain  and  picrocarmine  very 
beautiful  pictures  in  which  the  ova  are  stained  blue  and  the  cells  red  and 
yellow  with  picrocarmine  can  be  obtained.  A  very  instructive  lesson  in 
embryolog-y  is  furnished  by  the  ease  with  which  all  stages  of  development  of 
the  ova  from  the  simple  cell  up  to  the  developed  embryo  worm  can  be  fol- 
lowed in  these  preparations. 

5.  From  the  dog: 

Taenia  cucumerina.  This  is  by  far  the  most  common  tape-worm  of  the 
dogs  used  for  experiment  in  the  laboratory,  being  found  in  sixty  per  cent  of 
these  animals. 

Taenia  serraia.  Here  are  specimens  produced  by  feeding  dogs  Cysticeri 
pisiformes  from  the  rabbit. 

Taenia  ecltinococcus  was  found  only  in  dogs  artificially  fed  with  the  echi- 
nococcus  from  the  hog. 

Eiistrongyhts  gigas.  Here  is  a  specimen  of  this  worm,  95  cm.  long,  found 
free  in  the  peritoneal  cavity  of  a  dog.  It  has  been  found  three  times  in  this 
situation  in  dogs  used  for  experiment  in  the  laboratory. 

Strongylus  of  dochmius  trigonocephalus  {Uncinaria  trigonocepltala). 
This  parasite  was  found  in  the  small  intestine  in  seventy  per  cent  of  the 
dogs  used  in  the  laboratory,  a  nmch  larger  proportion  than  has  hitherto 
been  observed.  The  head  of  the  worm  was  often  found  imbedded  in  the 
mucous  membrane  and  surrounded  by  a  small  extravasation  of  the  blood. 
Sometimes  scanty,  it  was,  in  many  cases,  found  in  large  numbers.  Positive 
evidence  that  the  parasite  was  the  cause  of  anaemia  in  the  animals  could  not 
be  found.  It  was  occasionally  met  with  in  the  stomach  as  well  as  in  the  small 
mtestine. 

Tricocephalus  depresmisculus.  This  worm  appears  to  be  a  constant  inhab- 
itant of  the  dog's  caecum. 

Ascari'i  marginata  (doubtless  a  variety  of  Ascaris  mystax).  This  para- 
site was  found  in  only  a  few  cases.  It  was  found  both  in  the  stomach  and  in 
the  small  intestine. 

Filiaria  immitis.  It  was  not  met  with  in  any  of  the  dogs  used  in  the 
pathological  laboratory  and  is  not  common  in  this  region.  It,  however, 
occurs  here  and  it  has  been  observed  occasionally  in  the  biological  laboratory 
of  the  Johns  Hopkins  University. 

6.  From  the  rabbit: 

Coccidium  ovifoniie.  This  parasite  was  present  in  one-third  of  the  rabbits 
used  for  experiment  in  the  laboratory.  Coccidia  are  also  common  in  the 
intestines  of  rabbits.  There  are  small,  opaque,  grayish  white  patches,  sug- 
gesting somewhat  a  superficial  necrosis,  on  the  surface  of  the  mucous  mem- 
brane of  the  small  and  large  intestine.  These  patches  contain  large  numbers 
of  coccidia,  often  enclosed  in  epithelial  cells. 

Cysticercus  pisiformis.  It  is  common  in  the  peritoneal  cavity.  Here  are 
specimens  which  illustrate  the  nodules  and  scars  caused  by  the  migration  of 
this  parasite  through  the  rabbit's  liver. 

7.  From  the  rat: 

Cydicercus  fasciolaris.    It  was  found  in  the  liver. 


540  EXHIBITION  OF  ANIMAL  PARASITES 

8.  From  the  cat: 

Taenia  drassicollis.    This  worm  was  found  in  the  intestines. 

No  instance  of  Distoma  in  the  animals  examined  was  discovered  and  in 
general  distomatosis  of  domestic  animals  appears  to  be  rare  in  this  region. 
Throu'di  the  kindness  of  Professor  Brooks,  I  am  in  possession  of  a  number 
of  living  water  snails,  many  of  which  are  infested  with  cercaria  and  living 
specimens  of  those  interesting  forms  in  the  life  history  of  Distoma  are  exhib- 
ited under  the  microscope.  These  snails  were  obtained  in  the  neighborhood 
of  Baltimore,  so  that  opportunity  for  infection  with  distomata  is  present 
here. 


INTESTINAL  AND  HEPATIC  ACTINOMYCOSIS,  ASSOCIATED 
WITH  LEUKAEMIA' 

I.  Abstract  of  Clinical  History  by  Thomas  S.  Latimer 

History. — W.  H.  Thomas,  colored  male,  aged  21,  single,  a  day-laborer, 
was  admitted  to  the  City  Hospital,  Baltimore,  November  17,  1895.  The 
patient  claimed  to  have  always  been  well  until  the  previous  eight  months, 
during  which  several  attacks  simulating  appendicitis,  but  without  operative 
treatment,  occurred.  On  admission  he  complained  of  headache,  loss  of 
appetite  and  obstinate  constipation,  with  frequent  nose  bleed,  an  irregular 
fever,  slight  chills  and  sweats,  not  requiring  continuous  taking  to  bed. 

Examination. — The  patient  was  anaemic.  There  was  slight  enlargement 
of  the  axillary  and  post  cervical  lymphatic  glands.  The  chest  examination 
was  negative  except  for  a  feeble  heart-beat.  The  pulse  was  120  per  minute, 
weak  and  easily  compressible.  On  abdominal  examination,  no  tenderness  or 
lump  in  tlie  region  of  tlie  appendix  was  made  out.  Upon  repeated  examina- 
tion, the  spleen  could  not  be  felt.  His  liver,  however,  was  found  greatly 
enlarged,  extending  well  below  the  margin  of  the  ribs,  felt  smooth  and  firm 
and  was  somewhat  tender  on  palpation.  No  fluctuation  could  be  found. 
Because  of  a  tentative  diagnosis  of  deep  seated  hepatic  abscess,  the  liver  was 
aspirated  in  several  places  but  without  result.  No  microscopical  examina- 
tion of  the  small  particles  that  were  found  clinging  to  the  aspirator  was 
made.  Blood  examination  showed  red  blood  cells,  3,200,000,  white  blood 
cells,  24(),000.    A  differential  white  blood  count  showed: 

Polymorphonuclear  neutrophilic  leucocytes 58  per  cent. 

Polymorpho-nuclear  neutrophilic  leucocytes 5     "       " 

Large  mononuclear  and  transitional  leucocytes 4     "       " 

Small  mononuclear  leucocytes 3     "        " 

Myelocytic  leucocytes 30     "       " 

The  haemoglobin  was  25  per  cent.    No  malarial  parasites  were  found. 

Subsequent  Course. — The  patient  had  an  irregular  morning  and  evening 
temperature  that  varied  between  97.6°  and  104°  F.  respectively.  The 
patient  only  suffered  discomfort  when  lying  on  the  riglit  side  or  during 

^  Report  of  a  pathological  specimen. 
In:    A  Case  of  Intestinal  and  Hepatic  Actinomycosis  in  Man,  Associated  with 
Leukaemia,  by  Thomas  S.  Latimer,  Baltimore. 

Tr.  Ass.  Am.  Physicians,  Phila.,  1896,  XI,  332-335. 

541 


542  INTESTINAL  AND  HEPATIC  ACTINOMYCOSIS 

manipulation  of  the  liver.  The  liver  continued  to  increase  steadily  and  uni- 
formly in  size,  with  no  localized  area  of  tenderness,  fluctuation  or  enlarge- 
ment. The  patient  hecanie  unable  to  lie  on  the  right  side.  He  was  uncom- 
fortable after  eating  and  his  bowels  continued  constipated.  At  first  a  slight 
general  anasarca  developed,  Avhicli  rapidly  increased,  together  with  an 
ascites,  so  that  respiration  became  considerably  embarrassed.  The  dyspnoea 
was  greater  than  was  fairly  to  be  accounted  for  by  the  interference  with  the 
movements  of  the  diaphragm.  The  ascites  was  tapped  several  times  to  re- 
lieve the  dyspnoea.  Oedema  of  the  lungs  greatly  increased  the  dyspnoea. 
There  was  no  intestinal  disturbance  except  a  tendency  to  constipation  with- 
out increase  of  pain  on  defecation.  Any  disease  of  the  appendix  was  com- 
pletely masked  by  the  condition  of  the  liver,  ascites  and  oedema  of  the 
abdominal  wall.  In  spite  of  all  treatment,  the  patient's  strength  steadily 
diminished  until  February  10,  189G,  when  he  died,  apparently  from  asthenia. 

Viagnos'is. — Myelogenous  leukaemia  with  enlarged  liver  due  to  diffuse 
leukaemic  infiltration.    No  suspicion  of  actinomycosis  was  entertained. 

Autopsy  (by  N.  G.  Keirle  and  John  Rurah). — Autopsy  about  five  hours 
after  death;  body  that  of  a  medium  sized  man;  with  general  anasarca; 
oedema  greater  on  the  left  side  of  the  body,  the  face  and  arms  especially.  Skin 
pitted  on  pressure  everywhere;  the  al)domcn  much  distended  with  fluid; 
thin  watery  fluid  ran  from  the  nose  and  mouth.  The  muscles  were  pale  and 
bloodless.  The  abdomen  contained  a  large  quantity  of  pale,  straw-colored 
fluid ;  there  were  numerous  adhesions ;  both  the  parietal  and  visceral  layers 
of  the  peritoneum  generally  thickened;  intestines  bound  together  by  peri- 
toneal adhesions ;  omentum  very  adherent  and  without  fat.  Liver  extended 
some  10  cm.  below  the  margin  of  the  ribs.  Along  the  costal  margin  to  7  cm. 
of  the  median  line  was  a  dense,  firm  mass  of  organized  inflammatory  tissue 
3  cm.  in  thickness.  At  the  lower  part  of  the  same,  pus  escaped,  on  cutting 
out  the  mass  from  a  cavity  that  could  not  be  well  determined,  as  it  was  all 
closed  in  by  thick  walls  of  inflammatory  tissue.  Just  below  the  liver  about 
25  c.  c.  of  greenish  pus  escaped  from  an  abscess  at  that  point.  Spleen  was 
slightly  enlarged;  weight  350  gm ;  surface  bluish  gray;  capsule  slightly 
thickened.  Kidneys  were  somewhat  swollen  (moist)  witii  cloudy  swelling. 
The  entire  ascending  colon  and  the  hepatic  half  of  the  transverse  colon 
were  massed  in  inflammatory  tissue.  The  ascending  colon,  for  6  cm.  in  its 
midflle  could  not  be  removed.  The  appendix  was  involved  in  a  mass  of 
inllanimatory  tissues  just  above  the  brim  of  the  pelvis;  bile  duct,  patent; 
the  liver  weighed  3*-i(;0  gm.  Left  pleural  cavity  contained  500  c.  c.  of  pale, 
yellowish  fluid;  no  adhesions.  There  was  no  effusion  on  the  right  side; 
but  a  few  adhesions,  that  Ijrokc  up  easily,  between  visceral  and  parietal  layer 
of  the  lower  lobe  and  the  (li;iphragin.    The  right  lung  was  pushed  up  to  the 


ASSOCIATED  WITH  LEUKAEMIA  543 

fourth  rib  in  front,  but  extended  in  the  back  to  the  tenth-rib.  The  left  lung 
was  slightly  pigmented,  upper  lobe  crepitated,  was  somewhat  emphysema- 
tous, and  oozed  white  frothy  fluid  on  section.  Lower  lobe  did  not  creditate 
in  the  lower  half,  and  oozed  a  thin  sanious  fluid  on  section.  Pieces  sank  in 
water.  The  right  lung  showed  changes  similar  in  character  to  those  existing 
in  the  left  lung.    The  heart  showed  no  important  alteration. 

II.  Pathological  Repoet  of  Liver 

The  liver  was  the  only  part  submitted  to  me  for  examination.  It  had  been 
incised,  but  was  complete.    It  was  preserved  in  alcohol. 

Macroscopic  Examination. — The  liver  presents  an  irregularly  globular 
shape,  measuring  ;i2  x  18  x  12  cm.  The  right  lobe,  which  is  much  enlarged, 
is  occupied  throughout  nearly  its  whole  extent  by  a  mass  measuring  13  x  16 
cm.  This  mass  extends  for  a  short  distance  also  in  the  left  lobe.  It  extends 
throughout  the  whole  thickness  of  the  liver,  from  the  lower  to  the  upper 
surface,  but  it  occupies  a  larger  transverse  area  in  the  lower  two-thirds  than 
in  the  upper  third  of  the  organ. 

Tlie  inferior  surface  of  the  right  lobe,  with  the  exception  of  a  narrow 
margin  of  liver-substance  on  the  right  side,  is  entirely  occupied  by  the  new 
growth,  which  here  was  apparently  continuous  with  an  abscess  formation 
extending  downward  along  the  ascending  colon.  This  inferior  surface  and 
the  posterior  margin  of  the  right  lobe  are  connected  with  a  dense  mass  of 
fibrous  adhesions,  in  which  are  included  the  hepatic  vessels,  the  right 
adrenal  gland,  and  the  hepatic  flexure  of  the  colon. 

The  diaphragm  is  firmly  adherent  to  the  superior  surface  of  the  right  lobe 
of  the  liver,  and  has  been  removed  with  the  liver.  The  mass  of  new  growth 
in  the  liver  has  penetrated  through  the  liver  substance  on  the  upper  surface, 
but  has  not  penetrated  through  the  adherent  and  thickened  diaphragm. 

Upon  section  it  is  seen  that  a  definite  fibrous  capsule  of  dense  consistence 
and  grayish  color  surrounds  the  mass  in  the  liver,  separating  it  from  the 
surrounding  brownish  red  parenchyma  of  the  liver.  This  fibrous  capsule  is 
complete  except  in  certain  areas  on  the  inferior  surface  of  the  liver  or  of  the 
new  growth,  where  the  opaque,  yellowish  characteristic  foci  of  the  mass  come 
to  the  surface,  aixl  were  evidently  in  connection  with  the  subhepatic  abscess. 
This  relation  and  the  general  topography  afford  presumptive  evidence  that 
the  morbid  process  invaded  the  liver  from  below  by  continuity. 

Upon  section  the  mass  presents  in  exquisite  manner  the  characteristic 
honeycombed  appearance  of  a  chronic  actinomycotic  tumor.  There  are 
spaces  and  interlacing  trabeculae.  The  spaces  often  anastomose.  They  vary 
in  shape  and  size  on  section,  some  being  round,  others  oval,  others  more  or 
less  cylindrical.     They  contain  a  soft  yellowish  white  purulent  material, 


544  INTESTINAI^  AND  HEPATIC  ACTINOMYCOSIS 

which  can  be  squeezed  out  readily,  and  in  which  can  be  detected  abundantly 
tiie  small  yellowish  granules  of  the  colonies  of  actinomyces.  The  immediate 
margins  of  the  spaces  are  of  an  opaque,  yellowish  white,  necrotic  appear- 
ance.   The  spaces  vary  from  1  to  6  or  8  mm.  in  diameter. 

The  trabeculae  are  in  general  broad  and  interlacing  and  of  firm  consistence 
and  translucent  gray  color,  like  fibrous  or  granulation  tissue. 

Microscopic  Examination. — For  the  study  of  the  histological  structure, 
staining  with  haematoxylin  and  eosin  was  used ;  for  the  details  of  the  struc- 
ture of  tiie  parasite.  Gram's,  Weigert's,  and  ^lallory's  stains  Avere  found  most 
serviceable. 

The  microscopical  sections  show  interlacing  bands  of  fibrillated  connective 
tissue,  rich  in  long  fusiform  cells.  Between  these  fibrous  bands  there  are 
dense  accumulations  of  cells.  In  the  immediate  neighborhood  of  the  actino- 
myces the  cells  are  closely  packed  togetlier  and  there  is  little  or  no  basement 
substance.  These  cells  are  predominately  polymorphonuclear  leucocytes; 
in  other  words,  the  parasitic  colonies  lie  for  the  most  part  in  purulent  foci. 
Outside  the  areas  of  actual  pus  there  is  granulation  tissue  in  varying  stages 
of  formation,  from  a  tissue  composed  almost  exclusively  of  granulation  cells 
and  leucocytes  to  a  tissue  rich  in  basement-substance  and  Avitli  elongated 
cells.  In  the  fibrous  trabeculae  are  bloodvessels  with  thick  muscular  walls 
and  containing  an  excess  of  leucocytes,  among  which  are  many  mononuclear 
forms.  Adjacent  to  the  liver  parenchyma  the  fibrous  tissue  is  dense  and  con- 
tains numerous  rows  of  compressed  liver  cells,  presenting  the  appearance  of 
the  so-called  newly  formed  bile  ducts.  Here  and  there  are  mucous  glands 
derived  from  those  in  the  walls  of  the  bile  ducts,  but  now  without  evident 
connection  with  bile  ducts,  and  apparently  hypertrophied  and  proliferating 
so  as  to  simulate  adenomata.  The  capillaries  of  the  liver  contain  an  excess 
of  leucocytes,  mononuclear  cells  predominating. 

The  colonies  of  actinomyces  are  rarely  single,  more  frequently  they  are 
conglomerated  into  irregular  masses,  which  may  be  1  to  2  mm.  in  diameter. 
These  colonies  in  general  present  a  central,  looser  part  of  tangled  fine  fila- 
ments and  slender  rods,  with,  at  times,  deeply  staining  coccus-like  bodies, 
and  a  more  densely  w^oven  ring  of  fine  filaments  nearer  the  periphery,  from 
which  the  filamentous  branching  threads  radiate  outward.  These  radiating 
threads  often  extend  out  among  the  surrounding  pus  cells  and  are  often 
devoid  of  any  bulbous  swellings  or  club-like  extremities. 

It  is  not  found  easy  to  demonstiate  satisfactorily  the  clubs  which  are 
frequently  found  at  the  extremities  of  the  threads  in  cases  of  actinomycosis. 
The  stain  recommended  by  Mallory  is  most  suitable  for  this  demonstration. 
By  this  stain  there  couhl  be  demonstrated  around  some,  although  not  around 
most,  colonics  a  deeply  stained  red,  almost  homogeneous,  peripheral  zone. 


ASSOCIATED  WITH  LEUKAEMIA  545 

into  which  the  blue  threads  could  be  traced.  This  red  margin  clearly  be- 
longed to  the  parasite  and  not  to  the  surrounding  cells,  from  which  it  was 
often  separated  by  a  narrow  space.  The  outer  surface  of  this  red  border  was 
often  somewhat  irregular  and  indented,  and  in  general  the  impression  was 
gained  that  this  outer  zone,  which  stained  by  Mallory's  method  deeply  red, 
consisted  of  the  coalesced  material  which  composes  the  club-like  swellings 
at  the  extremities  of  the  threads  in  most  cases  of  actinomycosis.  I  am  in- 
clined to  interpret  the  failure  to  demonstrated  sharply  defined  clubs  in  this 
case,  and  the  appearance  of  a  diffuse,  homogeneous,  peripheral  substance, 
with  the  staining  reactions  of  the  clubs,  to  postmortem  changes.  That  the 
clubs  may  become  indistinct  or  even  disappear  in  consequence  of  postmortem 
changes  has  been  demonstrated  by  Weigert. 

But  only  some  of  the  colonies  showed  this  homogeneous  marginal  zone. 
Many  were  entirely  devoid  of  such  a  zone  or  of  any  suggestion  of  clubs.  It  is 
now  well  known  that  actinomyces  colonies  are  often  devoid  of  characteristic 
club-like  swellings.  In  this  case,  as  in  that  reported  by  Mallory,  there  are 
numerous  bacilli  belonging  to  the  actinomyces,  scattered  among  the  cells 
independently  of  the  colonies.  Clumps  of  streptococci  were  also  observed  in 
small  nimiber,  so  that  there  was  mixed  infection  with  actinomyces  and 
streptococcus. 

The  mass  in  the  liver,  therefore,  presents  macroscopically  and  micro- 
scopically the  typical  structure  of  an  actinomycotic  tumor.  As  has  already 
been  stated,  the  evidence  is  that  the  parasite  gained  access  to  the  liver  and 
generated  the  new  growth  at  the  inferior  surface  of  the  organ.  The  process 
gradually  extended  so  as  to  invade  most  of  the  right  lobe  and  a  part  of  the 
left  lobe  of  the  liver. 

Although  I  have  not  had  the  opportunity  to  examine  other  parts  from 
this  case,  there  can  be  little  or  no  doubt,  in  the  light  of  the  clinical  history 
and  the  observations  made  at  the  autopsy,  and  in  similar  cases,  that  the 
portal  of  entry  of  the  parasite  was  the  intestine,  and  in  all  probability  the 
starting  point  was  actinomycotic  appendicitis  (possibly  colitis),  whence  the 
morbid  process  extended  upward  in  the  tissues  along  the  ascending  colon 
to  the  right  hypochondrium,  and  invaded  the  liver  at  its  lower  surface. 


PREVENTIVE 
MEDICINE 


MODES  OF  INFECTION"  * 

Mr.  President  and  Gentlemen,  Fellow-Members  of  the  Medico-Chirur- 
gical  Society. — When  honored  by  the  invitation  to  deliver  the  Annual  Ad- 
dress before  this  Society,  it  seemed  to  me  appropriate  to  select  a  subject 
relating  to  that  department  of  medicine  in  which  the  most  important  dis- 
coveries have  been  made  in  recent  times.  The  far  reaching  advances  in  our 
knowledge  of  the  causation  of  infectious  diseases  have  opened  up  new  fields 
of  view  in  so  many  and  in  so  various  directions,  that  I  have  been  somewhat 
in  doubt  as  to  what  phase  of  the  subject  it  would  be  most  profitable  for  us 
to  consider  on  the  present  occasion. 

The  time  has  gone  by  when  much  profit  is  to  be  derived  from  the  discus- 
sion of  that  very  general  and  hackneyed  theme,  the  germ  theory  of  disease; 
for  the  doctrine  thus  expressed  is  no  longer  a  theory,  and  there  is,  doubtless, 
no  one  competent  to  form  an  opinion  on  the  subject  who  does  not  believe 
that  certain  infectious  diseases  are  caused  by  microorganisms,  and  that  it  is 
a  logical  inference  that  the  other  diseases  of  this  class  are  produced  by  para- 
sitic organisms — although  there  may  be  differences  of  opinion  as  to  how 
far  this  doctrine  has  been  proven  for  individual  diseases. 

I  have  thought  that  it  might  be  of  interest  to  pass  in  review  certain  funda- 
mental ideas  concerning  infectious  diseases,  and  to  note  how  far  these  ideas 
have  been  modified  or  expanded  by  recent  discoveries. 

Many  of  these  ideas  are  by  no  means  of  recent  origin,  for  from  the  earliest 
times  onward  much  attention  has  been  devoted  to  the  investigation  of  epi- 
demic diseases,  and  particularly  of  their  causation.  The  conceptions  of 
contagium  and  of  miasm  are  almost  as  old  as  the  history  of  medicine  itself. 
Ancient  writers  have  recorded  their  belief  in  the  existence  of  infected  locali- 
ties, and  in  the  conveyance  of  epidemic  diseases  by  means  of  the  drinking 
water  and  of  the  air.  Individual  predisposition  to  infection,  as  well  as  pre- 
disposition according  to  time  and  to  place,  are  not  modem  ideas,  as  is  shown 
by  such  historical  terms  as  genius  epidemicus,  constitutio  pestilens.  The 
science  of  epidemiology  is  much  older  than  that  of  bacteriology,  and  has 
taught  us  much  concerning  the  causation  and  development  of  infectious 
diseases. 

The  question  arises :  Has  our  knowledge  concerning  the  origin  and  spread 
of  infectious  diseases  been  widened  and  has  it  become  more  exact  since  the 

^  Annual   address  delivered   before   the  Medical  and   Chirurgical   Faculty   of 
Maryland,  Baltimore,  April  27,  1887. 
Tr.  M.  and  Chir.  Fac.  Maryland,  Bait.,  1887,  67-87. 

549 


550  MODES  OF  INFECTION 

diseoverv  of  the  livinnf  eonta<;ium  of  many  of  these  diseases?  While  grant- 
iii"'  the  vast  scientific  importance  of  this  discovery,  it  is  in  itself  only  the 
confirmaton  of  the  faith  of  far-seeing  minds  of  past  generations.  The  mere 
demonstration  of  that  which  was  previously  a  reasonable  supposition  does 
not  offer  a  new  point  of  view. 

It  is  proper  for  us  to  inquire  wliether  the  investigation  of  the  micro- 
organisms causing  infectious  diseases,  and  the  study  of  the  characteristics 
and  life  histories  of  these  parasites,  of  the  media  and  conditions  of  their 
growth  and  of  the  means  of  their  destruction,  have  added  materially  to  the 
knowledge  which  was  already  afforded  us  by  the  epidemiological  study  of 
tiiese  diseases.  Have  we  tlierehy  gained  a  clearer  conception  of  such  terms 
as  miasm,  contagium,  and  miasmatic  contagium?  Have  we  a  deeper  insight 
into  the  conditions  under  which  a  virus  is  transmitted  from  an  infected  to  a 
healthy  person,  and  of  the  conditions  of  infection  through  the  air,  the  drink- 
ing water  and  other  media?  Can  we  form  any  more  definite  ideas  of  what  is 
meant  hy  individual  predisposition  to  an  infectious  disease  and  by  such 
terms  as  predisposition  in  time  and  in  place? 

p]ven  if  we  were  obliged  to  answer  all  of  these  questions  in  the  negative, 
not  one  particle  would  be  detracted  from  the  imiiortance  of  further  pursuit  of 
bacteriological  studies,  for  experience  has  shown  that  nothing  is  more  short 
sighted  than  to  estimate  the  value  of  scientific  discoveries  according  to  their 
immediate  practical  utility.  And,  moreover,  the  questions  which  I  have 
raised  relate  to  only  a  few  out  of  many  practical  aspects  of  these  studies; 
but  if,  as  I  believe  to  be  true,  it  can  be  shown  that  light  has  been  shed  upon 
some  of  the  most  interesting  and  obscure  ])roblems  concerning  infectious 
diseases,  by  the  -studies  of  the  living  organisms  causing  these  diseases,  then  it 
is  apparent  that  the  results  of  these  studies  are  of  more  immediate  interest 
and  of  interest  to  a  nmch  wider  circle  than  would  otherwise  be  the  case. 

Our  knowledge  in  the  directions  indicated  is  but  fragmentary.  The  title 
"  Modes  of  Infection  "  under  wliicli  I  wish  to  gather  together  some  of  these 
fragments  has  been  selected  as  a  convenient  one  to  cover  most  of  the  thougliis 
which  I  desire  to  present  to  you.  The  intention,  however,  is  not  to  consider 
exhaustively  all  possible  modes  of  infection,  but  chiefly  to  dwell  upon  such 
p(»ints  relating  to  the  causation  of  infectious  diseases  as  have  been  most 
illuminated  by  recent  investigations,  particularly  in  bacteriology. 

There  is  now  tolerable  unanimity  of  opinion  as  to  the  meaning  attached 
to  tile  terms  infections  and  infectious  diseases.  ^lost  recent  authorities 
understand  l)y  infection  the  condition  produced  by  the  entrance  and  multi- 
plication of  pathogenic  microorganisms  within  the  body.  An  infectious 
di.«ease  is  one  which  is  caused  l)y  the  invasion  and  reproduction  within  the 
body  of  pathogenic  microorganisms.     To  define  an  infectious  agent  as  a 


MODES  OF  INFECTION  551 

specific  poison  capable  of  indefinite  multiplication  is  only  to  express  ob- 
scurely the  idea  just  conveyed,  for  we  know  and  can  conceive  of  no  poison 
capable  of  indefinite  multiplication  except  a  living  organism.  The  analogies 
formerly  drawn  from  the  fermentation  and  the  putrefaction  of  organic  sub- 
stances, and  still  preserved  in  the  designation  zymotic  diseases,  have  lost  all 
force  as  an  opposing  argument  since  it  has  been  shown  that  these  processes 
are  produced  by  living  organisms.  In  the  absence  of  any  other  probable,  I 
may  say  even  conceivable,  hypothesis,  to  refuse  to  accept  the  doctrine  of  a 
contagium  vivum  as  applicable  to  all  infectious  diseases  because  it  has  been 
demonstrated  only  for  certain  of  these  diseases,  is  about  as  reasonable  as  to 
reject  the  law  omnis  cellula  e  celiida  because  this  has  not  been  proven  for 
every  cell  or  every  species  of  cell. 

We  should  be  by  no  means  justified  to  substitute  in  the  foregoing  defini- 
tion of  infection  instead  of  pathogenic  microorganisms,  bacteria  or  fissure 
fungi.  It  is  true  that  most  of  the  infectious  agents  with  which  we  have 
become  acquainted  are  bacteria,  but  the  malarial  parasite  is  a  notable  excep- 
tion to  this.  There  are  grounds  for  believing  that  the  specific  organisms  of 
some  of  the  infectious  diseases  may  belong  to  low  forms  of  animal  or  vege- 
table life  other  than  the  bacteria.  Our  means  for  demonstrating  the  pres- 
ence of  bacteria  are  comparatively  satisfactory,  but  this  cannot  be  said  of 
most  of  the  other  protozoa,  and  it  is  perhaps  in  consequence  of  this  imper- 
fection of  our  methods  of  investigation  that  so  many  infectious  diseases  have 
resisted  successfully  our  efforts  to  discover  their  efficient  causes. 

It  is  gratifying,  after  so  much  strife,  to  be  able  to  record  this  agreement 
of  opinion  as  to  the  definitian  of  infection  and  of  infectious  diseases  in 
general.  It  is  customary  to  classify  infectious  diseases  etiologically  into 
contagious,  miasmatic,  and  miasmatic  contagious  diseases.  As  to  the  signifi- 
cance of  these  terms,  and  particularly  as  to  the  real  nature  of  the  so-called 
miasmatic  contagious  diseases,  there  exists  great  confusion.  As  the  epithets 
miasmatic,  contagious,  and  miasmatic  contagious  meet  us  upon  every  hand 
in  our  investigations  of  infectious  diseases,  as  they  relate  to  conceptions 
which  lie  at  the  very  foundation  of  our  knowledge  of  the  subject,  it  is  mani- 
festly of  the  utmost  importance  that  their  meaning  should,  if  possible,  be 
rendered  clear  and  precise.  I  question,  however,  whether  these  terms  any 
longer  suffice  for  the  classification  of  infectious  diseases,  although,  as  Petten- 
kofer  has  said,  the  ideas  contagium  and  miasm  are  so  bred  into  our  flesh 
and  blood  that  we  would  as  soon  think  of  parting  with  them  as  with  one  of 
our  limbs  even  after  it  had  become  useless. 

Originally  the  distinction  between  contagium  and  miasm  was  sharply 
defined.  There  are  two  attributes  which  essentially  characterize  the  ordinary 
conception  of  contagium,  viz.  multiplication  within  the  diseased  body,  and 


552  MODES  OF  IiNrFECTION 

capability  of  transmission  from  the  diseased  to  the  healthy  body.  The  latter 
attribute  implies,  of  course,  the  elimination  of  the  contagious  principle  in 
an  active  state  from  the  diseased  body.  On  the  other  hand  a  miasm  is  pro- 
duced outside  of  the  body.  According  to  the  belief  of  many  writers  it  does 
not  multiply  within  the  body,  and  all  agree  that  it  is  not  eliminated  from 
the  body  in  a  condition  capable  of  producing  infection.  Especial  emphasis 
in  framing  these  distinctions  was  laid,  in  the  case  of  a  contagious  disease, 
upon  the  origin  of  the  virus  within  the  body  (endogenous),  and  in  the  case 
of  a  miasmatic  disease,  outside  of  the  body  (exogenous).  These  ideas  con- 
cerning contagium  and  miasm  answered  well  enough  for  the  typically  con- 
tagious diseases  such  as  syphilis  and  the  exanthematous  fevers,  and  for  the 
typically  miasmatic  disease,  malaria.  But  confusion  began  during  the  mid- 
dle third  of  the  present  century  when  the  origin  and  spread  of  Asiatic 
cholera  were  carefully  studied.  It  was  found  impossible  to  classify  this 
disease  under  either  of  the  two  existing  divisions.  It  has  in  common  with 
the  contagious  diseases  the  characteristic  that  persons  affected  with  cholera 
may  convey  the  disease  to  localities  previously  free  from  it,  and  may  prove 
the  starting  points  of  wide  spread  epidemics.  Cases  sometimes  occur  ©f 
which  the  only  natural  interpretation  is  that  they  have  originated  from  conta- 
gion. On  the  other  hand,  in  infected  localities  the  disease  often  develops  in 
those  who  have  never  seen  a  cholera  patient,  much  less  come  into  contact 
with  one,  while  those  in  attendance  upon  such  patients  as  a  rule  are  no  more 
liable  to  the  disease  than  others  living  in  the  same  locality.  Similar  observa- 
tions were  made  with  reference  to  typhoid  fever. 

There  arose  the  contest,  not  yet  ended,  between  the  contagionists  who 
held  that  these  diseases  are  to  be  ranked  as  contagious,  and  the  localists  who 
regarded  them  as  miasmatic  in  origin,  and  to  explain  certain  peculiarities 
introduced  the  new  conception  of  a  portable  miasm.  The  majority,  how- 
ever, sougiit  refuge  under  a  new  cover.  The  class  of  miasmatic  contagious 
diseases  was  formed,  and  in  this  amalgamated  group  were  placed  cholera, 
typhoid  fever,  yellow  fever,  and  several  other  infectious  diseases  not  con- 
veniently classified  elsewhere. 

Various  meanings  have  been  and  still  are  attached  to  the  term  miasmatic 
contagious  diseases.  Some  understand  by  a  miasmatic  contagious  disease 
one  which  is  propagated  sometimes  by  a  contagium  and  sometimes  by  a 
miasm — that  is,  sometimes  by  a  virus  produced  within  the  diseased  body, 
and  sometimes  by  a  virus  produced  outside  of  the  body.  Others  hold  the 
of)inion  that  for  the  production  of  cholera,  typhoid  fever,  and  other  diseases 
of  this  class,  two  viruses  or  microorganisms  are  necessary,  one  derived  from 
a  person  affected  with  the  disease,  and  the  other  derived  from  the  soil,  or  at 
least  from  some  external  source.     But  the  view  which  lias  gained  the  most 


MODES  OF  INFECTION  553 

adherents,  and  which  is  the  prevalent  one  at  the  present  time,  is  that  a 
patient  with  typhoid  fever  or  with  cholera  throws  off  from  his  body  a  poison, 
a  microorganism,  which  at  the  time  of  its  discharge  is  not  capable  of  pro- 
ducing the  disease,  but  which  under  favorable  circumstances  undergoes  out- 
side of  the  body  some  unknown  metamorphosis  by  which  it  acquires  this 
power.  This  last  view  is  the  one  which  is  accepted  in  most  of  the  text  books 
on  medicine  published  within  recent  years  in  this  country  and  in  Europe, 
and  I  presume  that  it  embodies  the  belief  on  the  subject  of  most  practitioners 
of  medicine. 

One  of  my  main  objects  in  the  present  address  is  to  direct  your  attention 
to  what  seem  to  me  weak  points  in  this  hypothesis,  and  to  endeavor  to  ex- 
plain in  a  more  natural  and  satisfactory  manner  the  pecuharities  of  the  so- 
called  miasmatic  contagious  diseases,  at  least  so  far  as  two  leading  represen- 
tatives of  this  group,  viz.  cholera  and  typhoid  fever,  are  concerned.  The 
discovery  of  the  microorganisms  which  are  in  all  probability  to  be  regarded 
as  the  specific  causes  of  cholera  and  of  typhoid  fever,  and  the  investigation 
of  their  properties,  should  have  led,  it  might  be  supposed,  to  a  general  re- 
vision of  the  widely  accepted  doctrine  of  miasmatic  contagious  diseases ;  but 
this  has  not  been  the  case — at  least  among  clinical  writers,  who  apparently 
see  no  reason  why  the  actually  discovered  germs,  as  well  as  those  previously 
surmised,  may  not  imdergo  the  assumed  matamorphosis  outside  of  the  body 
which  renders  them  capable  of  infection.  This  is  still  the  reasoning  of 
Liebemieister  in  his  work  on  "  Infectious  Diseases,"  published  in  1885,  in 
which  he  accepts  the  cholera  and  the  typhoid  bacilli  as  the  agents  of  infection. 

Let  us  now  examine  in  detail  the  arguments  which  are  brought  forward 
in  support  of  the  miasmatic  contagious  doctrine  as  previously  defined. 

In  the  first  place,  it  is  urged  that  a  metamorphosis  such  as  is  assumed  to 
occur  in  the  agents  of  infection  after  their  elimination  from  the  body  of  a 
cholera  or  a  typhoid  fever  patient,  has  its  analogy  in  the  well  known  in- 
stances of  alternation  of  generation ;  and  usually  the  ordinary  tape-worm  is 
cited,  the  ova  of  which,  as  is  well  known,  first  develop  into  cysticerci,  and  only 
these,  when  swallowed,  are  capable  of  giving  rise  to  mature  tape-worms. 

The  argument  by  analogy,  however,  instead  of  supporting  the  miasmatic 
contagious  hypothesis,  is  directly  opposed  to  it.  In  the  class  of  organisms 
to  which  the  typhoid  and  the  cholera  germs  belong,  no  instance  is  known  of 
any  organism  after  its  discharge  from  the  body  acquiring  infectious  proper- 
ties which  it  did  not  previously  possess,  or  of  its  undergoing  any  transforma- 
tion at  all  resembling  that  assumed  to  occur.  On  the  other  hand,  we  know 
of  some  pathogenic  organisms  which  are  rendered  more  virulent  by  their 
passage  through  the  body  of  an  animal  susceptible  of  the  disease;  and,  in 
general,  bacteriologists  are  inclined  to  regard  as  especially  potent  bacteria 
38 


554  MODES  OF  INFECTION 

which  are  fresh  from  the  bodies  of  infected  animals.  Where  it  is  aimed  to 
produce  intoxication  by  means  of  ptomaines,  as  can  be  done  by  cultures  of 
tlie  typhoid  and  of  the  cholera  bacilli,  then  it  is  true  that  old  cultures,  as 
would  naturally  be  supposed,  are  the  most  effective ;  but  there  is  no  reason 
to  believe  tliat  ptomaine  intoxication  plays  any  role  in  the  primary  infection 
with  the  typhoid  or  the  cholera  germs ;  or,  if  it  did,  where  are  the  ptomaines 
likely  to  be  more  abundant  than  in  fresh  typhoid  and  cholera  stools? 

Before  we  knew  as  much  as  we  now  do  about  the  properties  of  bacteria, 
the  transformation  hypothesis  now  under  criticism  could  be  advanced  with 
some  show  of  reason ;  but  at  present  our  information  upon  this  and  similar 
points  is  by  no  means  scanty,  and  in  the  absence  of  any  pertinent  analogy 
for  such  an  occurrence,  the  assumption  seems  entirely  unwarrantable  that 
the  specific  organisms  of  cholera  or  of  typhoid  fever  acquire  new  or  in- 
creased virulence  after  their  removal  from  the  body.  Inoculation  experi- 
ments upon  animals  with  the  cholera  spirilla  lend  no  support  to  this 
assumption. 

In  the  second  place,  it  is  urged  in  support  of  the  miasmatic  contagious 
theory  that  the  .specific  germs  of  these  diseases  cannot  be  eliminated  from  the 
body  in  a  condition  capable  of  causing  infection;  otherwise  those  who  are  in 
proximity  to  the  patients  must  frequently  become  infected,  as  in  cases  of 
smallpox  or  of  typhus  fever.  This  is,  evidently,  the  argument  which  has  the 
greatest  weight.  It  is  to  explain  the  absence,  or  at  least  the  infrequency  of 
any  direct  communication  of  cholera  and  of  typhoid  fever  from  one  person 
to  another,  that  the  hypothesis  under  consideration  was  constructed. 

It  is,  of  course,  apparent  that  the  specific  genus  of  cholera  and  of  typhoid 
fever  must  be  discharged  from  the  body  in  a  very  different  way  and  must 
have  very  different  properties  from  those  of  the  contagium  of  smallpox  and 
similar  diseases.  It  is  because  our  ideas  of  what  characterizes  a  contagium 
are  derived  from  our  observations  of  such  highly  contagious  diseases  as 
smallpox  or  scarlet  fever  that  we  are  loath  to  admit  that  cholera  or  typhoid 
fever  patients  emit  anything  which  can  be  called  an  active  contagium.  I 
believe,  also,  that  not  a  little  of  the  difficulty  of  this  admission  conies  from 
the  popular  notion  that  a  source  of  active  contagiofl  must  necessarily  infect 
the  surrounding  atmospliere,  as  is  the  case  with  a  smallpox  patient. 

It  is,  however,  possible  to  reconcile  the  fact  that  the  discharges  of  cholera 
and  of  typhoid  fever  patients  contain  a  contagium,  and  that,  too,  in  an 
active  form,  with  the  infrequency  with  which  these  diseases  are  communi- 
cated in  a  manner  which  is  ordinarily  understood  as  contagious. 

Let  us  take  for  example  cholera,  and  consider  in  the  light  of  recently 
a.'<certained  facts  what  conditions  nnist  be  fulfilled  in  order  that  the  disease 
may  bo  contracted  directly  from  a  patient.    It  is  to  be  borne  in  mind  that  the 


MODES  OF  INFECTION  555 

cholera  germ  is  discharged  from  the  body  only  in  the  faeces,  and  very  excep- 
tionally in  the  voniitus.  It  is  not  present  in  the  urine,  nor  in  the  breath, 
nor  in  the  sputum,  nor  Is  it  thrown  off  from  the  surface  of  the  body.  These 
are  well  established  facts,  so  that  we  can  conclude  that  the  only  danger 
of  direct  infection  from  a  cholera  patient  is  by  means  of  the  stools.  It 
is  necessary,  however,  to  come  into  actual  contact  with  the  stools  in  order 
to  become  thus  infected.  It  has  been  proven  by  exact  and  very  interest- 
ing experiments  of  Naegeli  and  Buchner  that  bacteria  are  never  lifted  by 
currents  of  air  from  the  surface  of  fluids  or  from  moist  surfaces  in  gen- 
eral. One  could  remain  in  a  room  cont-aining  any  quantity  of  cholera 
stools  swarming  with  cholera  spirilla  and  there  would  be  no  danger  of  infec- 
tion with  cholera  through  the  air.  Bacteria  are  conveyed  into  the  air  only 
when  they  are  in  a  dry  condition,  and  the  cholera  organism  is  quickly  des- 
troyed by  drying.  So  far  as  cholera  is  concerned,  there  is  therefore  no  basis 
for  the  prevalent  belief  that  the  atmosphere  becomes  infected  for  a  certain 
distance  around  substances  containing  an  active  contagium,  although  this 
belief  is  justified  as  regards  certain  other  species  of  contagia. 

But  it  does  not  suffice  for  infection  merely  to  have  come  into  contact  with 
cholera  stools ;  portions  of  the  stools  must  actually  be  swallowed.  There  is 
every  reason  to  believe  that  infection  with  cholera  takes  place  only  through 
the  reception  of  the  virus  directly  into  the  alimentary  canal,  and  not  through 
subcutaneous  inoculation  or  through  the  respiratory  organs. 

If  this  last  condition  be  fulfilled  and  portions  of  cholera  stools  be  actually 
swallowed,  even  then  in  any  given  case  the  chances  are  probably  at  least  three 
to  one  that  no  infection  would  follow;  for  cholera  ispirilla  are  destroyed  by 
the  acid  of  the  gastric  juice,  and  it  is  a  matter  of  experience  that  only  a 
minority  of  those  exposed  to  the  specific  cause  actually  contract  the  disease. 
These  considerations  show  how  worthless  are  the  isolated  experiments  of 
those  foolhardy  individuals  who  have  voluntarily  swallowed  cholera  dejecta 
and  cultures  of  the  cholera  spirilla.  Whatever  had  been  the  outcome  of  these 
few  experiments,  no  positive  conclusions  could  be  drawn  from  them.  A 
negative  result,  for  reasons  already  given,  was  to  be  expected;  a  positive 
result  would  prove  nothing,  for  the  experiments  were  all  made  in  districts 
already  infected  with  cholera,  and  it  would  have  been  impossible  to  decide 
whether  the  infection  had  taken  place  in  a  natural  way  or  as  the  result  of  the 
experiment.  The  conditions  were  of  course  entirely  different  in  the  instance 
of  the  doctor  in  Koch's  laboratory  who  contracted  cholera  as  a  result  of  care- 
less handling  of  cultures  of  cholera  spirilla,  for  there  was  at  the  time  no 
cholera  in  Germany  and  no  other  possible  source  of  infection  than  the 
cultures. 


556  MODES  OF  INFECTION 

Enou"-h  has  been  said  to  show  what  difficulties  attend  the  direct  com- 
munication of  the  disease  by  a  cholera  patient.  It  is  perfectly  explicable 
why  direct  contagion  is  so  infrequent  notwithstanding  the  fact  that  cholera 
stools  contain  the  contagion  in  an  active  form,  indeed  sometimes  almost  as 
a  pure  culture.  There  is  no  necessity  to  resort  to  any  such  artificial,  compli- 
cated and  unsupported  hypothesis  as  the  miasmatic  contagious  doctrine  in 
the  sense  at  present  under  consideration. 

But  any  satisfactory  explanation  the  specific  cause  of  cholera  must  account 
for  occasional  instances  of  transmission,  of  the  disease  by  contagion.  I  do 
not  propose  to  discuss  here  in  detail  that  most  vexed  question.  Is  cholera 
contagious?  but  I  believe  that  he  who  denies  absolutely  the  contagiousness 
of  the  disease  must  shut  his  eye  to  plain  facts.  There  are  instances,  and 
of  course  they  are  to  be  sought  not  in  regions  wliere  cholera  is  epidemic  but 
where  sporadic  cases  occur,  where  the  only  natural  interpretation  is  in  favor 
of  direct  contagion. 

Now  the  miasmatic  contagious  hypothesis  has  no  room  for  these  contagious 
cases,  whereas  there  is  no  difficulty  in  accounting  for  occasional  instances  of 
contagion  according  to  the  view,  which  I  believe  to  be  an  established  fact, 
that  the  cholera  stools  contain  the  active  cholera  virus.  Indeed,  such  in- 
stances of  contagion  are  to  be  expected,  although  least  frequently  of  course 
among  doctors  and  nurses,  whose  comparative  immunity  is  usually  cited  to 
prove  the  non  existence  of  any  active  contagium  eliminated  by  a  cholera 
patient.  Doctors  and  nurses  are  the  most  likely  to  see  that  the  cholera  stools 
are  properly  disinfected,  and  also  to  disinfect  their  hands  or  other  parts  of 
their  persons  which  may  have  become  soiled  by  the  dejecta.  On  the  other 
hand,  among  ignorant  persons  living  in  cramped  and  unclean  quarters  the 
chances  of  direct  contagion  are  mucli  more  favorable.  It  is  probable  that  the 
statements  in  books  relating  to  the  frequency  of  cases  of  cholera  caused  by 
contagion  are  misleading,  for  such  cases  are  least  likely  to  come  under  the 
ol)servation  of  those  who  contribute  most  largely  to  medical  literature, 
namely,  physicians  with  practice  in  hospitals  and  among  the  well-to-do 
classes  living  under  good  hygienic  surroundings. 

There  is  a  general  agreement  upon  the  point  that  the  epidemic  spread  of 
cholera  cannot  be  accounted  for  by  direct  contagion.  It  is  generally  admit- 
ted that  the  specific  agent  of  infection,  derived  from  the  dejecta  of  a  cholera 
I)atient,  may  under  favorable  conditions  multiply  outside  of  the  body,  in  the 
ground,  upon  vegetables  and  elsewhere.  We  are  to  seek  the  chief  sources  of 
infection  in  cholera  epidemics  in  the  drinking  water,  the  food,  the  ground, 
in  actual  contact  with  sul)stances  containing  the  specific  germs.  A  discus- 
sion of  these  various  external  sources  of  infection,  notwithstiinding  the 
great  interest  and  inijHjrtance  of  the  subject,  is  not  pertinent  to  my  present 


MODES  OF  INFECTION  557 

argument,  which  is  to  show  not  only  that  it  is  not  necessary  to  deny  the 
existence  of  an  active  contagium  in  the  fresh  cholera  stools,  but  that  there  is 
every  reason  to  believe  that  such  contagium  is  actually  present. 

I  have  selected  cholera  for  the  purpose  of  showing  the  falseness  of  the  mias- 
matic contagious  theory  as  expounded  by  Liebermeister  and  others,  partly 
because  our  knowledge  concerning  its  etiology  has  become  much  more 
exact  since  Koch's  discovery  of  its  specific  germ,  and  partly  because  this 
disease  has  been  generally  regarded  as  the  main  support  of  this  theory. 
Indeed,  the  hypothesis  of  the  transformation  or  ripening  of  germs  after 
they  leave  the  body  was  constructed  especially  to  account  for  the  phenomena 
of  Asiatic  cholera.  The  arguments  which  I  have  presented  apply  equally  to 
typhoid  fever,  another  important  member  of  the  miasmatic  contagious  group 
of  diseases.  Here,  too,  the  specific  virus  is  eliminated  from  the  body,  as  a 
rule,  only  in  the  faeces.  There  exist  the  same  reasons  in  the  one  as  in  the 
other  disease  why  infection  is  likely  to  take  place  only  exceptionally  in  the 
form  of  direct  contagion.  It  is  not  necessary  to  go  over  the  same  ground 
with  typhoid  fever  which  we  have  already  traversed  with  cholera,  for  as 
regards  the  point  now  under  consideration  the  evidence  is  of  the  same  char- 
acter for  both  diseases. 

Our  information  is  at  present  wholly  insufficient  to  enable  us  to  form  any 
positive  opinion  as  to  the  mode  of  elimination  of  the  specific  virus  of  yellow 
fever. 

I  have  attempted,  gentlemen,  to  make  it  probable  that  a  patient  with 
chelera  or  with  typhoid  fever  emits  a  contagium  in  just  as  active  a  state  as  a 
patient  with  smallpox  or  with  scarlet  fever.  We  cannot  explain  the  difference 
in  frequency  with  which  the  two  sets  of  diseases  are  propagated  by  direct 
contagion  by  assuming  that  only  in  the  latter  diseases  is  the  virus  eliminated 
in  a  condition  capable  of  producing  infection.  The  relative  frequency  with 
which  infectious  diseases  are  communicated  by  direct  contagion  depends,  I 
believe,  first  of  all,  upon  tlie  channels  through  which  the  virus  is  eliminated 
from  the  body. 

It  may  be  stated  as  a  broad  proposition  that  every  infectious  disease  can  by 
artificial  means  be  transmitted  from  an  individual  affected  with  the  disease 
to  another  individual  susceptible  of  the  disease.  This  is  only  the  natural 
inference  from  the  fact  that  each  infectious  disease  has  its  specific  virus  in 
the  shape  of  a  microorganism  which  is  present  and  multiplies  in  the  bodies 
of  those  affected  with  the  disease.  Although  there  is  no  evidence  that  under 
natural  conditions  malaria  is  ever  transmitted  from  one  person  to  another, 
still  it  is  possible  to  accomplish  this  artificially,  as  has  been  proven  by  the 
experiments  of  such  trustworthy  observers  as  Gerhardt  and  Marchiafava 
and  Celli,  who  inoculated  successfully,  with  blood  from  malarious  patients, 
persons  who  were  entirely  free  from  malaria. 


558  MODES  OF  INFECTION 

Strictly  speaking,  therefore,  in  every  infectious  disease  there  is  a  conta- 
gium,  hut  we  should  fall  into  grave  errors  if  we  drew  our  conclusions  as  to  the 
natural  modes  of  infection  from  the  results  of  artificial  inoculations,  as  is 
illustrated  hy  the  example  of  malaria. 

To  explain  why,  under  natural  conditions,  some  diseases,  such  as  the  ex- 
anthematous  fevers,  are  usually  transmitted  by  contagion;  other  diseases, 
such  as  typhoid  fever  and  cholera,  only  infrequently,  and  other  diseases, 
such  as  malaria,  never  by  contagion,  it  is  necessarj-,  I  repeat,  to  consider  the 
channels  by  which  the  virus  is  eliminated,  if  at  all,  from  the  body. 

If,  as  in  the  case  of  malaria,  the  virus  is  not  discharged  at  all  from  the 
body,  then  of  course  there  is  no  possibility,  under  the  conditions  of  nature, 
of  the  communication  of  the  disease  from  one  person  to  another.  If,  as  in 
the  case  of  cholera  and  of  typhoid  fever,  the  virus  is  discharged  only  by  way 
of  the  faeces,  then  contagion  is  possible,  but  it  is  not  likely  to  occur  with 
ordinary  care  and  with  ordinarj'  cleanliness.  If,  as  in  the  case  of  scarlet 
fever,  measles  and  smallpox,  the  virus  is  eliminated  from  the  skin  and  ad- 
heres to  thin  scales  of  epidermis  which  can  be  readily  transported  through 
the  air,  then  contagion  is  likely  to  be  a  common  occurrence. 

I  do  not  wish  to  be  understood  as  implying  that  the  mode  of  elimination 
of  a  virus  is  the  sole  factor  in  determining  the  degree  of  contagion  of  a  dis- 
ease. There  are,  of  course,  other  important  factors,  such  as  the  degree  of 
resistance  offered  by  the  virus  to  drying,  the  chances  of  its  being  conveyed 
into  the  air,  its  quantity,  etc.,  as  well  as  the  degree  of  susceptibility  which 
exists  on  the  part  of  those  exposed  and  the  portal  through  which  the  virus 
must  enter  in  order  to  cause  infection. 

I  trust,  gentlemen,  that  this  will  be  found  a  more  rational,  fruitful  and 
satisfactory'  way  of  regarding  the  infectious  diseases  than  to  wander  among 
the  nuizes  of  miasmatic,  contagious,  and  miasmatic  contagious  diseases,  and 
to  imagine  that  in  some  diseases  the  virus  is  eliminated  in  a  potent  state, 
and  in  other  diseases  in  a  state  requiring  some  subsequent  transformation 
to  make  it  potent. 

It  is  unfortunate  that  our  positive  knowledge  concerning  the  mode  of 
elimination  from  the  body  of  the  specific  poisons  of  the  various  infectious 
diseases  is  still  very  incomplete.  Only  for  those  diseases  whose  special 
agents  of  infection  have  been  discovered  is  our  information  exact  upon  this 
point.  For  some  other  diseases  we  have  good  grounds  for  forming  an  opinion, 
while  in  the  case  of  several  infectious  diseases,  such  as  relapsing  fever,  we 
are  quite  in  the  dark  on  the  subject. 

It  may  not  be  out  of  place  to  call  your  attention  to  certain  points  wliich 
boar  upon  this  question.  The  experiments  of  Wyssokowitsch,  made  in  the 
Hygienic  I^il)oratory  of  Gottingen,  and  published  not  quite  a  year  ago,  have 
shown  that  nonpathogenic  bacteria  injected  into  the  blood  of  animals  in  a 


MODES  OF  INFECTION  559 

few  hours  disappear  from  the  blood  and  are  deposited  in  certain  organs, 
especially  the  liver,  the  spleen,  and  the  marrow  of  the  bones,  whence  they 
also  disappear,  as  a  rule,  in  a  short  time.  They  are  not  eliminated  by  the 
urine  or  by  any  other  excretion.  He  found  that  microorganisms  in  general 
are  discharged  by  the  urine  only  when  they  form  some  local  lesion  in  the 
kidney  or  some  part  of  the  urinary  tract.  He  found,  likewise,  that  organisms 
injected  into  the  blood  are  not  discharged  by  the  intestine  unless  they  first 
cause  some  lesion  of  the  alimentary  canal.  Similar  facts  were  determined 
regarding  secretions  from  other  mucous  membranes.  The  experiments  of 
Wyssokowitsch  warrant  the  following  statements: 

The  specific  germs  of  infectious  diseases  can  be  and,  in  cases  of  recovery, 
doubtless  often  are,  destroyed  within  the  body. 

Contrary  to  what  many  have  believed,  the  kidneys  and  the  intestines 
cannot  be  regarded  as  important  means  of  freeing  the  body  from  micro- 
organisms which  have  gained  access  to  the  blood. 

When  the  specific  microorganisms  of  an  infectious  disease  are  found  in 
the  urine  or  in  the  faeces,  it  may  be  inferred  that  the  genito-urinary  appara- 
tus and  the  alimentary  tract  respectively  are  the  seat  of  some  lesion  produced 
by  these  organisms. 

These  experiments  justify  also  the  inference,  in  itself  probable  enough, 
that  the  specific  viruses  of  infectious  diseases  are  discharged  from  those  free 
surfaces  which  are  themselves  the  seats  of  the  characteristic  lesions  of  the 
disease,  as  for  instance  from  the  respiratory  tract  in  pulmonary  tubercu- 
losis, lobar  pneumonia,  whooping  cough,  diphtheria;  from  the  skin,  in  scar- 
let fever,  measles,  smallpox,  typhus  fever,  erysipelas;  from  the  intestines, 
in  typhoid  fever,  cholera ;  from  the  urethra  or  vagina  in  gonorrhoea,  syphilis. 
For  several  diseases,  however,  we  have  no  satisfactory  data  for  determining 
in  what  manner  the  special  poison  is  eliminated.  Tliis  is  true,  for  instance, 
of  cerebrospinal  fever  and  relapsing  fever. 

We  are  ignorant  as  to  whether  microorganisms  may  be  eliminated  by 
the  breath,  although  it  is  a  common  notion  that  this  occurs.  In  view  of  the 
experiments  already  cited,  which  show  the  difficulty  with  which  micro- 
organisms are  detached  from  moist  surfaces  by  currents  of  air,  it  seems  im- 
probable that  organisms  can  be  conveyed  from  the  body  by  the  breath.  Of 
course,  if  the  organisms  were  momentarily  set  free  by  acts  of  coughing,  tlien 
they  might  be  carried  on  by  the  respiratory  current,  but  it  is  at  least  very 
questionable  wliether  in  ordinary  breathing  particulate  substances  can  be 
thus  transmitted. 

We  have  up  to  this  point,  gentlemen,  considered  only  the  diseased  body 
and  its  fresh  excreta  as  the  source  of  infection,  and  we  have  reached  the 
conclusion  that  in  every  infectious  disease  there  is  a  contagium,  but  that 
whether  or  not  the  disease  is  likely  to  be  propagated  as  a  contagious  one 


560  MODES  OF  INFECTION 

depends  upon  various  circumstances,  among  which  the  mode  of  elimination 
of  the  contagium  from  the  body  is  of  the  utmost  importance. 

A  question  of  great  interest,  as  well  as  of  practical  importance,  is  whether 
or  not  any  given  infectious  agent  finds  conditions  outside  of  the  body  favor- 
able for  its  prolonged  existence.  This  question  is  not  identical  with  that  of 
the  reproduction  of  the  special  virus  outside  of  the  body.  The  importance  of 
the  latter  point  has  been  somewhat  exaggerated  in  discussions  relating  to  the 
etiology  of  infectious  diseases.  Special  agents  of  infection  may  be  widely 
distributed  without  their  finding  conditions  favorable  to  reproduction  out- 
side of  the  animal  body.  Thus  the  bacillus  of  tuberculosis  appears  to  be 
almost  as  widely  spread  throughout  nature  as  the  organisms  which  cause 
suppuration,  and  yet  the  tubercle  bacillus  can  find  only  exceptionally  the 
conditions  of  temperature  and  of  nutriment  which  permit  its  multiplication 
outside  of  the  body,  whereas  the  pus  organisms  doubtless  find  abundant 
opportunities  for  their  development  on  various  substances  outside  of  the 
body. 

The  mere  facts  of  the  wide  distribution  of  certain  infectious  microorgan- 
isms and  of  frequent  infection  from  external  sources  do  not  justify  us  in 
drawing  conclusions  as  to  the  capability  of  growth  of  the  organisms  as 
saprophytes.  This  is  a  point  which  can  be  positively  decided  only  by  a 
knowledge  of  the  life  history  and  properties  of  the  different  infectious 
organisms. 

So  far  as  our  present  knowledge  reaches,  it  is  only  such  infectious  micro- 
organisms as  form  spores  which  are  capable,  under  natural  conditions,  of 
prolonged  existence  outside  of  the  body  without  reproduction.  These  spores 
can  resist  high  temperatures,  drying,  and  various  other  agencies  which  are 
destructive  to  the  ordinary  vegetative  cells.  Thus  we  can  explain  why,  for 
instance,  infection  with  the  tubercle  bacillus  can  take  place  from  external 
sources,  while  infection  with  gonorrhoea  always  requires  contact  with  fresh 
gonorrhoeal  secretion,  although  in  neither  instance  does  the  special  virus 
n'produce  itself  outside  of  the  animal  body,  except  under  such  artificial 
conditions  as  we  can  produce  in  our  laboratories. 

The  question  as  to  the  reproductfon  of  infectious  microorganisms  outside 
of  the  body,  although  it  has  not  all  of  the  significance  sometimes  attached 
to  it,  is  nevertheless  one  of  much  interest.  It  is  from  this  point  of  view  that 
infectious  microorganisms  are  often  classified  by  bacteriologists.  Thus  there 
are  microorganisms  which  find  only  witliin  tlie  animal  body  the  conditions 
suitable  for  their  growth  and  development.  Such  organisms  are  called 
obhgatory  parasites.  Examples  are  the  parasitic  organisms  of  syphilis, 
gonorrhoea,  tuberculosis,  and  doubtless  of  smallpox,  measles,  scarlet  fever, 
etc.    Other  infectious  microorganisms  are  capable  of  growing  under  natural 


MODES  OF  INFECTION  561 

conditions  both  within  the  body  and  outside  of  the  body,  as  in  the  soil.  Such 
infectious  agents  are  called  by  bacteriologists  potential  parasites.  In  the 
case  of  some  of  the  potential  parasites  their  natural  home  seems  to  be  the 
animal  body,  as  appears  to  be  true,  at  least  in  most  localities,  of  cholera 
spirilla  and  typhoid  fever  bacilli ;  while  in  other  cases  the  natural  habitat  of 
the  organism  is  the  soil,  whence  it  makes  occasional  excursions  into  the 
animal  body.  The  malarial  parasite  conforms  to  the  latter  type.  The  growth 
of  microorganisms  outside  of  the  body  is  spoken  of  as  saprophytic. 

In  the  case  of  typhoid  fever  there  is  no  a  priori  objection  to  supposing 
that  its  parasite  may  grow  in  situations  where  it  has  not  been  introduced  by 
any  human  being.  The  weight  of  evidence  seems  certainly  opposed  to  such 
a  supposition ;  still  Murchison  and  other  authorities  have  contended  for  the 
so-called  spontaneous  origin  of  typhoid  fever  in  some  cases,  and  the  question 
can  be  settled  only  by  a  careful  analysis  of  epidemiological  facts,  in  the  in- 
terpretation of  which  tliere  inhere,  as  is  well  known,  important  sources  of 
error. 

Of  the  utmost  importance  in  the  elucidation  of  the  spread  of  many  of  the 
infectious  diseases,  particularly  of  cholera  and  of  typhoid  fever,  is  the  in- 
vestigation of  the  conditions  favorable  to  the  existence  and  growth  of  para- 
sitic microorganisms  in  the  soil,  the  drinking  water,  upon  vegetables  and 
other  substances  outside  of  the  body,  as  well  as  of  the  means  by  whifch  infec- 
tion occurs  from  these  external  sources.  These  subjects,  which  pertain  to 
public  hygiene,  can  be  touched  upon  only  very  briefly  upon  this  occasion. 

More  attention  has  been  paid  to  the  influence  of  the  soil  and  of  the  drink- 
ing water  in  the  propagation  of  epidemic  diseases  than  to  any  other  of  the 
factors  named.  Under  the  brilliant  leadership  of  Pettenkofer  a  school  of 
hygienists  has  developed  who  lay  emphasis  almost  exclusively  upon  the  soil 
in  this  matter,  and  are  unwilling  to  admit  that  epidemic  infection  takes 
place  through  the  drinking  water. 

We  owe  to  this  school  valuable  researches  as  to  the  physical  conditions  of 
the  soil  which  favor  the  development  into  an  epidemic  of  such  diseases  as 
cholera  and  typhoid  fever,  as  well  as  to  conditions  hostile  to  such  develop- 
ment. Among  the  conditions  favorable  to  an  epidemic  may  be  mentioned 
a  certain  degree  of  porosity  of  the  soil,  a  certain  amount  of  moisture,  and 
some  impregnation  with  decomposing  animal  and  vegetable  material.  But 
notwithstanding  these  painstaking  investigations,  which  are  much  more 
extensive  than  this  brief  notice  would  indicate,  it  must  be  admitted  that 
they  have  left  us  considerably  in  the  dark  as  to  how  we  are  to  regard  the 
soil  as  concerned  in  the  propagation  of  infectious  diseases.  There  has  been 
no  actual  demonstration  of  the  infectious  microorganisms  of  cholera  and 
of  typhoid  fever  in  the  soil,  or  of  their  multiplication  there,  and,  above  all, 


562  MODES  OF  INFECTION 

no  satisfactx)ry  explanation  as  to  the  means  by  which  infectious  agents  are 
transported  from  the  soil  to  the  animal  body. 

To  the  medical  profession  in  this  country  and  in  England  it  is  not  com- 
prehensible how  there  can  still  be  distinguished  authorities  who  deny  that 
epidemics  of  typhoid  fever  or  of  cholera  are  ever  attributable  to  drinking 
water.  Yet  in  Germany  there  are  hygienists  who  are  not  only  quite  posi- 
tively, but  even  somewhat  violently  opposed  to  what  they  call  the  drinking 
water  hypothesis.  It  is  doubtless  true  that  we  are  often  too  ready  to  accuse 
the  drinking  water  in  an  outbreak  of  typhoid  fever ;  but  if  medical  evidence 
is  worth  anything,  there  can  be  no  reasonable  doubt  that  many  epidemics 
of  typhoid  fever  have  been  due  to  contamination  of  the  drinking  water 
with  the  typhoid  virus. 

The  experiments  of  Meade  Bolton  have  revealed  the  important  fact  that 
most  patliogenic  microorganisms  do  not  multiply  in  water  sufficiently  pure 
ever  to  be  used  for  drinking  purposes.  Not  only  do  the  pathogenic  bacteria 
not  multiply  in  drinking  water,  but,  if  they  do  not  contain  spores,  most  of 
them  are  destroyed  in  drinking  water  in  a  short  time,  varying  from  a  few 
hours  to  several  days,  according  to  the  species  and  the  quantity  of  bacteria. 
These  experiments  have  been  hailed  by  the  Munich  school  of  hygienists  as 
opposed  to  the  view  that  epidemic  infection  can  take  place  through  the 
drinking  water,  but  they  need  not  be  so  interpreted,  nor  are  they  so  inter- 
preted by  Bolton. 

These  experiments  make  it  necessary  to  suppose  that  a  single  infer^tion 
of  the  drinking  water  with  infectious  organisms  would  not  suffice  for  an 
epidemic  lasting  more  than  a  few  days.  To  keep  up  a  long  continued  epi- 
demic by  means  of  contaminated  drinking  water,  there  must  be  some  com- 
munication between  the  water  and  some  focus  in  which  the  disease  producing 
organisms  are  present  in  large  number  or  are  multi])lying.  This  is  in 
harmony  with  the  fact  that  repeatedly  in  epidemics  traceable  to  the  water, 
communications  have  been  proven  to  exist  between  the  water  and  cess  pools, 
drains,  privies,  or  other  possible  foci  of  infection.  In  considering  water  as 
a  source  of  infection,  one  must  remember  that  this  can  occur  not  only  by 
drinking,  but  also  by  the  use  of  the  water  in  cooking,  and  in  washing  dishes 
subsequently  used  to  contiiin  food. 

As  is  well  known,  there  have  been  several  epidemics  of  typhoid  fever  in 
which  the  source  of  infection  has  been  traced  to  the  milk.  Although  in 
these  instances  it  was  believed  that  the  milk  was  itself  infected  by  the  addi- 
tion of  contaminated  water,  nevertheless  it  is  well  to  note  that  in  one  im- 
portant particular  milk  differs  from  water  in  its  Ix^havior  toward  pathogenic 
microorganisms.  Milk  is  an  excellent  nutritive  medium  for  nearly  ail  of 
these  organisms.    The  tvphoid  and  the  cholera  spirilla  grow  in  milk  rapidly 


MODES  OF  INFECTION"  563 

and  abundantly,  without  producing  any  alteration  in  the  external  appearance 
of  the  milk.  Inasmuch  as  certainty  of  infection  depends,  in  the  case  of  many 
diseases,  upon  the  number  of  organisms  which  enter  the  body,  it  is  apparent 
that  this  property  imparts  a  particularly  dangerous  character  to  infected 
milk. 

As  regards  the  means  of  transportation  by  which  the  agents  of  infection 
are  conveyed  from  external  objects  to  the  body,  the  most  important  is  be- 
lieved to  be  the  air  by  those  who  lay  the  most  stress  upon  the  influence  of  the 
soil  in  the  spread  of  epidemic  diseases.  It  seems  probable,  however,  that  too 
big  a  role  has  hitherto  been  assigned  to  the  air  as  a  carrier  of  contagion.  The 
fact  has  already  been  mentioned  that  currents  of  air  are  incapable  of  lifting 
bacteria  from  moist  surfaces ;  and  Naegeli  has  shown,  also,  that  if  bacteria 
be  dried  with  their  natural  gelatinous  envelopes  or  from  albuminous  sub- 
stances, they  are  in  much  the  same  physical  condition  as  insects  attached  to 
a  surface  by  mucilage,  and  cannot  be  carried  away  by  the  air  unless  they  are 
first  converted  into  a  dust-like  powder.  If  it  be  furthermore  considered  that 
some  bacteria  are  destroyed  by  complete  desiccation,  it  is  evident  that  these 
facts  compel  us  to  restrict  within  much  narrower  limits  than  most  writers 
have  done,  the  importance  of  the  air  in  the  transportation  of  agents  of  in- 
fection. Still  there  remains  evidence  enough  that  the  virus  of  some  diseases, 
notable  of  malaria,  and  probably  of  yellow  fever,  may  be,  and  often  is,  con- 
veyed through  the  atmosphere.  As  infection  through  the  air  is  something 
which  we  have  no  means  of  combating,  it  is  encouraging  to  learn  that  this 
resistless  fate  has  a  narrower  sway  than  we  had  been  led  to  believe. 

There  are  many  grounds  for  supposing  that  the  chief  means  of  infection 
are  by  actual  contact,  in  one  way  or  another,  with  the  agents  of  infection. 
The  conviction  of  the  truth  of  this  statement  is  borne  in  almost  irresistibly 
upon  one  who  has  engaged  extensively  in  the  cultivation  of  microorganisms. 
I  have  kept  for  weeks  at  a  time,  side  by  side  in  a  sterilized  dish  to  which 
filtered  air  had  free  access,  two  watch  glasses,  one  containing  a  culture  of 
the  typhoid  bacilli  in  beef  tea,  the  other  containing  simply  sterilized  beef  tea. 
During  this  time,  notwithstanding  its  close  proximity  to  the  typhoid  culture, 
the  beef  tea  in  the  second  glass  remained  perfectly  pure,  without  a  trace  of 
contamination  from  its  neighbor.  Many  illustrations  of  the  same  principle 
might  be  drawn  from  the  work  of  a  bacteriological  laboratory.  We  study 
the  exposed  cultures  of  such  pathogenic  organisms  as  anthrax  bacilli,  cholera 
spirilla,  glanders  bacilli,  and  run  no  risk  of  infection  from  these  so  long  as 
we  do  not  come  into  contact  with  the  cultures. 

There  is  one  observation  which  we  sometimes  make  in  our  laboratories  in 
summer — to  our  discomfiture — which,  although  it  may  seem  trivial,  is  not 
without  its  practical  bearings.     This  is  the  readiness  with  which  micro- 


5G4  MODES  OF  INFECTION 

organisms  may  be  disseminated  by  flies  and  other  insects.  Upon  the  so- 
called  plate  cultures  we  can  sometimes  trace  the  devious  wanderings  of  an 
inj^ect  by  the  colonies  of  microorganisms  which  it  has  planted  in  its  course. 
The  application  of  this  experience  to  a  possible  means  of  transportation  of 
the  special  organisms  of  infectious  disease  is  too  apparent  to  need  further 
elucidation. 

I  shall  not  weary  you  by  attempting  to  elaborate  in  all  of  its  details  the 
doctrine  that  one  of  the  chief  means  of  infection  is  by  contact.  There  are 
thousands  of  ways  in  which  we  can  inadvertently  come  into  contact  with 
sources  of  infection.  This  teaches  us  that  it  is  an  error  to  construct  ex- 
clusive theories  of  infection,  such  as  are  expressed  by  the  terms  "  soil  hy- 
pothesis," "  drinking  water  hypothesis,"  etc. 

There  is  one  lesson,  however,  which  has  come  from  the  epidemiological 
study  of  the  relations  of  the  soil  and  of  the  drinking  water  to  infectious 
diseases,  and  that  is  the  immense  importance  of  the  proper  disposal  of  the 
refuse  matter  around  human  habitations  and  the  supply  of  pure  drinking 
water.  The  efficacy  of  a  good  system  of  drainage  or  of  sewerage  in  prevent- 
ing the  development  of  many  epidemic  diseases  is  probably  to  be  sought,  not 
in  the  purifying  of  the  ground  so  that  pathogenic  organisms  cannot  grow 
there,  but  in  affording  means  by  which  these  organisms,  contained  in  human 
excreta  and  other  substances,  are  readily  carried  away.  The  discussion  of 
these  points  relates  to  sanitary  science,  and  does  not  belong  to  my  theme, 
bnt  I  cannot  refrain  from  a  brief  allusion  to  the  subject  on  account  of  its 
great  practical  importance. 

What  can  be  more  instructive,  as  well  as  more  encouraging,  than  to  wit- 
ness the  manner  in  which  Asiatic  cholera,  during  its  present  journey,  has 
failed  to  secure  any  foothold  in  those  European  cities  which  are  characterized 
by  cleanliness  and  proper  sanitary  arrangements,  although  it  has  been  re- 
peatedly introduced  into  such  cities?  These  cities  have  secured  their  im- 
munity, not  by  spasmodic  precautionary  efforts  after  the  entrance  of  the 
disease,  but  at  the  price  of  systematic,  vigilant  and  intelligent  exertions 
during  what  may  be  termed  the  time  of  peace.  Without  wishijig  to  pose  as 
an  alarmist,  I  believe  that  with  the  announcement  of  the  appearance  of 
Asiatic  cholera  upon  this  continent,  the  time  has  come  to  emphasize  the  fact 
that  the  only  enlightened  and  civilized  public  policy  is  to  be  prepared  at  all 
times  and  in  all  phues  to  meet  the  enemy. 

Of  the  various  factors  entering  into  the  causation  of  infectious  diseases 
none  is  more  obscure  than  that  designated  predisposition,  and  yet  this  is  a 
factor  with  which  wc  must  undoubtedly  reckon.  This  mysterious  predis- 
position to  certain  infectious  diseases  plays,  perhaps,  even  a  greater  role  with 
u«,  at  the  present  time,  than  it  did  with  our  forefathers  in  medicine,  who 
w  roto  80  much  concerning  corustitutio  epidemica. 


MODES  OF  INFECTION  565 

It  cannot  be  said  that  the  increase  in  our  knowledge  concerning  the  specific 
causes  of  infectious  diseases  has  illuminated  to  any  great  extent  what  is 
meant  by  predisposition,  and  still  a  few  glimmers  of  light  have  been  sent  into 
this  dark  corner  by  recent  bacteriological  investigations. 

Mention  has  already  been  made  of  the  fact  that  the  cholera  spirilla  are 
destroyed  by  the  acid  gastrc  juice,  so  that  we  are  warranted  in  regarding  all 
conditions  which  neutralize  the  acidity  of  the  gastric  juice  as  affording  pre- 
disposition to  this  disease. 

Perhaps  the  most  positive  addition  to  our  knowledge  in  this  direction  has 
been  the  demonstration  of  the  importance  of  preexisting  diseases  or  lesions 
of  structure  in  affording  ready  means  of  ingress  and  suitable  conditions  for 
the  lodgment  and  growth  of  pathogenic  microorganisms  within  the  body. 
In  this  connection  attention  may  be  called  to  the  experiments  of  Wyssoko- 
witsch  and  of  Prudden,  which  show  the  necessity  of  previous  alterations  of 
structure  in  the  cardiac  valves  before  they  are  adapted  for  the  lodgment  and 
development  of  the  microorganisms  which  cause  ulcerative  endocarditis. 
Grawitz  has  shown  that  the  bacteria  of  suppuration  may  be  injected  in  large 
quantity  into  the  healthy  peritoneal  cavity  without  doing  any  damage,  but 
that  they  set  up  suppurative  peritonitis  if  they  meet  there  wounded  tissues, 
stagnating  fluids,  or  so-called  dead  spaces  from  which  they  are  not  readily 
absorbed. 

Especially  instructive  in  this  light  is  the  study  of  the  manifold  compli- 
cations which  attend  scarlet  fever,  typhoid  fever,  and  other  diseases  which 
are  accompanied  by  necroses  and  ulcerations  of  the  mucous  membranes  of 
the  throat,  intestine,  and  other  parts  with  which  microorganisms  axe 
normally  in  contact.  While  it  has  been  shown  that  most  of  these  micro- 
organisms are  harmless,  there  are  not  infrequently  among  them  some  which 
are  pathogenic,  such  as  the  cosmopolitan  bacteria  of  suppuration.  The 
superficial  necroses  and  ulcerations  of  the  mucous  membranes  in  scarlet  fever 
and  typhoid  fever  afford  means  of  ingress  for  these  bacteria,  which  often  find 
within  the  body  foci  of  least  resistance  resulting  from  the  existing  diseases. 
We  are  therefore  not  surprised  to  learn  that  many  of  the  complications  of 
these  diseases  are  produced  by  the  staphylococci  and  streptococci  of  suppu- 
ration, or  that  there  are  frequently  found  in  these  diseases  in  the  tissues  and 
fluids  bacteria,  particularly  micrococci,  which  have  nothing  to  do  with  the 
specific  cause  of  the  primary  disease,  although  often  enough  mistaken  for  it 
by  hasty  observers. 

Time  will  not  permit  me  to  elaborate  the  ideas  here  touched  upon. 
Enough  has  been  said  to  show  that  we  need  not  despair  of  gaining  some 
definite  conception  as  to  the  nature  of  predisposition  and  immunity  to  dis- 
ease, but  we  must  not  forget  that  our  positive  knowledge  at  present  touches 


566  MODES  OF  INFECTION 

only  the  outlying  boundaries  of  the  subject.  We  do  not  even  know  why  dif- 
ferent species  of  animals  behave  differently  toward  infectious  agents — why, 
for  instance,  house  mice  resist  the  deadly  glanders  bacilli,  while  the  more 
hardy  field  mice  readily  succumb — still  less  can  we  account  for  differences 
in  susceptibilty  of  individuals  of  the  same  species. 

It  is  easy  enough  to  construct  plausible  theories  of  predisposition  and  of 
immunity,  and  such  theories  have  their  scientific  uses;  but  we  must  remem- 
ber that  we  have  gained  no  explanation  of  the  facts  when  we  base  our  theories 
upon  such  popular  phrases  as  struggle  for  existence  between  cells  and  bac- 
teria, or  fitness  of  the  soil  for  the  growth  of  bacteria,  etc.  Even  the  more 
tangible  phagocytic  doctrine  of  Metschnikoft'  cannot  be  said  to  have  materi- 
ally advanced  our  knowledge  as  yet,  or  to  have  met  with  much  support  in 
facts. 

Before  leaving  this  subject  it  may  be  well  to  say  that  possibly  we  are  at 
present  in  the  habit  of  assigning  too  great  importance  to  predisposition  as 
a  factor  in  the  causation  of  infectious  diseases.  It  is  such  a  convenient  refuge 
that  we  are  tempted  to  bury  in  its  obscurity  many  etiological  facts  which  we 
cannot  readily  explain.  While  I  would  not  by  any  means  ignore  the  impor- 
tance of  hereditary  predisposition  to  tuberculosis,  Is  it  not  probable  that 
cases  are  often  included  in  this  category  which  do  not  belong  there  ?  When 
we  think  of  the  especial  dangers  of  infection  to  which  the  offspring  of  tuber- 
culous parents  are  exposed  from  their  youth  upward,  of  the  likelihood  that  a 
child  will  follow  an  occupation  which  has  favored  the  development  of  phthisis 
in  a  parent,  and  of  the  frequency  with  which  the  concurrence  of  the  disease  in 
ancestor  and  descendant  is  mere  coincidence,  it  is  apparent  that  we  are  in 
danger  of  assigning  to  heredity  a  larger  part  in  the  causation  of  tuberculosis 
than  it  deserves. 

It  must  be  admitted  that  the  instances  in  which  we  have  been  able  by  exper- 
iments upon  animals  of  the  same  species  to  demonstrate  different  degrees 
of  j)re(lisposition  toward  infectious  agents  are  not  very  striking  or  very 
numerous. 

And  now,  gentlemen,  I  bring  to  conclusion  this  imperfect  survey  of  some 
j)oints  relating  to  the  etiology  of  infectious  diseases.  We  are  only  upon  the 
threshold  of  a  deeper  insight  into  the  nature  of  a  class  of  diseases  which  have 
been  more  devastating  to  the  human  race  than  any  uj)heavals  of  nature  or 
any  wars.  They  have  left  their  imprint  upon  political,  the  social  and  the 
intellectual  history  of  the  world.  One  need  not  be  of  a  very  sanguine  tem- 
perament to  hope  that  our  steadily  increasing  knowledge  will  bear  fruit,  not 
only,  as  in  the  past,  in  the  prevention  of  these  diseases,  but  also  in  a  rational 
system  of  casual  therapeutics. 


CONSIDERATIONS  CONCERNING  SOME  EXTERNAL  SOURCES 

OF  INFECTION  IN  THEIR  BEARING  ON 

PREVENTIVE  MEDICINE' 

No  department  of  medicine  has  been  cultivated  in  recent  years  with  such 
zeal  and  with  such  fruitful  results  as  that  relating  to  the  causes  of  infectious 
diseases.  The  most  important  of  these  results  for  preventive  medicine  and 
for  the  welfare  of  mankind  is  the  knowledge  that  a  large  proportion  of  the 
causes  of  sickness  and  death  are  removable. 

It  is  evident  that  efforts  to  preserve  health  will  be  most  intelligently  and 
jcffectually  applied  when  they  are  based  upon  an  accurate  and  full  knowledge 
ofjthie_agencies  which  cause  disease.  Public  and  private  hygiene,  however, 
cannot  and  fortunately  has  not  waited  for  the  full  light  of  that  day,  whose 
dawn  has  only  begun  to  appear,  when  we  shall  have  a  clear  insight  into  the 
causation  of  preventable  diseases.  Cleanliness  and  comfort  demand  that 
means  shall  be  taken  to  render  pure  the  ground  on  which  we  live,  the  air 
which  we  breathe,  and  the  water  and  food  with  which  we  are  supplied,  and 
we  must  meet  these  needs  without  waiting  to  learn  just  what  relation  in- 
fectious agents  bear  to  the  earth,  air,  water  and  food. 

It  is  a  fortunate  circumstance  that  modern  sanitation  has  been  controlled 
so  largely  by  the  belief  in  the  dependence  of  endemic  and  epidemic  diseases 
upon  organic  impurities  in  the  soil  and  in  the  water.  Incomplete  and  even 
erroneous  in  many  respects  as  are  the  views  which  have  prevailed  concerning 
the  origin  and  spread  of  epidemic  diseases  by  the  decomposition  of  organic 
substances,  the  sanitary  measures  which  have  been  directed  toward  the  re- 
moval of  filth  have  achieved  great  conquests  in  limiting  the  development  and 
extension  of  many  infectious  diseases.  The  benefits  which  one  common- 
wealth of  this  country  has  derived  from  the  intelligent  employment  of  public 
sanitary  measures  were  clearly  and  forcibly  presented  before  this  Association 
last  year  by  Dr.  Walcott  in  his  admirable  address  in  State  Medicine. 

While  nothing  should  be  said  or  need  be  said  to  lessen  the  importance  of 
cleanliness  for  public  health,  it  is  important  to  bear  in  mind  that  hygienic 
cleanliness  and  aesthetic  cleanliness  are  not  identical.  In  water,  which 
meets  the  most  severe  chemical  tests  of  purity,  typhoid  bacilli  have  been 
found.     On  the  other  hand,  the  air  in  the  Berlin  sewers,  which  certainly 

^  An  address  in  State  Medicine  delivered  before  the  American  Medical  Asso- 
ciation, Newport,  R.  I.,  June  28,  1889. 

Maryland  M.  J.,  Bait,  1889,  XXI,  201-208;    226-234. 

567 


508  EXTERNAL  SOURCES  OF  IXFECTION 

does  not  meet  the  most  modest  demands  of  aesthetic  cleanliness,  has  been 
found  to  be  nearly  or  quite  free  from  bacteria. 

It  needs  only  to  be  stated  to  be  generally  admitted  that  the  scientific  basis 
of  preventive  medicine  must  be  the  accurate  knowledge  of  the  causative 
ao-ent^  of  preventable  diseases,  a  knowledge  which  can  be  derived  only  from 
a  careful  study  of  all  the  properties  of  these  agents,  the  modes  of  their  recep- 
tion and  of  their  elimination  by  the  body,  the  circumstances  which  favor  and 
those  which  retard  or  prevent  their  development  and  spread,  their  behavior 
in  the  various  substances  which  surround  us  or  which  we  take  into  our 
bodies,  and  the  sources  of  infection,  not  only  those  which  laboratory  experi- 
ments sliow  to  be  possible,  but  those  which  are  actually  operative. 

So  long  as  we  were  unacquainted  with  the  living  organisms  causing  in- 
fection, tlie  means  at  our  disposal  for  studying  the  etiology  of  infectious  dis- 
eases were  limited  to  the  observation  of  all  of  the  circumstances  which  we 
could  determine  regarding  the  origin  and  spread  of  these  diseases.  We 
could  only  infer  what  might  be  the  properties  of  the  infectious  agents  from 
the  study  of  phenomena  often  obscure  and  difficult  of  interpretation. 
Chiefly  by  this  method  of  investigation  the  science  of  epidemiology  has  been 
built  up.  It  has  established  facts  and  laws  no  less  of  practical  than  of  scien- 
tific importance.  But  it  has  left  unsolved  many  problems,  and  has  filled 
gaps  with  speculations.  Admitted  epidemiological  facts  are  often  open 
to  various  interpretations. 

We  are  evidently  at  a  great  advantage  when  we  can  study  the  epidemiologi- 
cal facts  with  a  knowledge  of  the  substances  which  actually  cause  infection, 
and  this  we  are  now  enabled  to  do  for  a  limited  number  of  the  infectious 
diseases.  This  new  method  of  research,  which  thus  far  has  been  mainly 
bacteriological,  has  aided  us  not  so  much  by  simplifying  the  problems  of 
etiolog}',  which  still  remain  complicated  enough,  as  by  affording  greater 
accuracy  to  the  results. 

It  is  my  aim  in  this  address  to  consider  some  results  of  the  modern  studies 
of  pathogenic  microorganisms  in  their  bearing  upon  preventive  medicine, 
more  particularly  upon  the  sources  of  infection.  It  is,  of  course,  impossible 
within  the  limits  of  the  address  to  attempt  a  complete  survey  of  this  impor- 
tant field.  Time  will  permit  the  presentation  of  only  some  of  the  salient 
points. 

Infectious  diseases  are  those  which  are  caused  by  the  multiplication  within 
the  body  of  puthogonic  microorganisms. 

It  has  always  been  recognized  that  some  infectious  diseases,  such  as  the 
exanthematous  fevers,  are  conveyed  directly  from  the  sick  to  the  healthy.  It 
is  not  disputed  that  in  these  evidently  contagious  diseases  the  infectious 
gem)  in  discharged  from  the  body  in  a  state  capal)le  at  once  of  giving  rise  to 
infection. 


BEAEING  ON  PREVENTIVE  MEDICINE  569 

In  a  second  group  of  infectious  diseases,  of  which  malaria  is  the  type,  the 
infected  individual  neither  transmits  the  disease  to  another  person  nor,  so 
far  as  we  know,  is  capable  of  infecting  a  locality.  Here  there  is  reason  to 
believe  that  the  infectious  germ  is  not  thrown  off  in  a  living  state  from  the 
body,  but  is  destroyed  within  the  body.  In  this  group  the  origin  of  infection 
imder  natural  conditions  is  always  outside  of  the  body. 

In  a  third  group  there  is  still  dispute  whether  the  disease  can  be  trans- 
mitted directly  from  person  to  person,  but  all  are  agreed  that  the  infected 
individual  can  infect  a  locality.  It  is  especially  fortunate  that  the  bacteria 
which  cause  cholera  and  typhoid  fever,  the  two  most  important  representa- 
tives of  this  group  of  so-called  miasmatic-contagious  diseases,  have  been  dis- 
covered and  isolated  in  pure  culture.  These  are  the  diseases  about  whose 
origin  and  epidemic  extension  there  has  been  the  greatest  controversy.  They, 
above  all  other  diseases,  have  given  tlie  impulse  to  public  sanitation  during 
the  last  half  century.  The  degree  of  success  with  which  their  extension  in 
a  community  is  prevented  is  an  important  gauge  of  the  excellence  of  the 
local  .sanitary  arrangements.  A  clear  comprehension  of  the  origin  and 
spread  of  these  diseases  signifies  the  solution  of  many  of  the  most  vexed  and 
important  problems  of  epidemiology  and  of  state  hygiene. 

It  is  difficult  to  understand  how  those  who  accept  the  discovery  that  the 
bacteria  causing  typhoid  fever  and  cholera  have  been  found  and  cultivated 
from  the  stools  of  patients  affected  with  these  diseases,  can  doubt  that  these 
patients  are  possible  sources  of  contagion  or  can  entertain  the  view  once  so 
widely  prevalent  that  the  infectious  germs  of  these  diseases  are  discharged 
from  the  body  in  a  condition  incapable  of  producing  immediate  infection. 
In  an  address  delivered  on  another  occasion  I  have  endeavored  to  present 
the  considerations  which  reconcile  the  comparative  infrequency  of  direct 
contagion  for  these  diseases  with  the  belief  in  the  elimination  of  the  causative 
germs  in  an  active  state  from  the  body,  and  have  there  pointed  out  several 
well  known  factors  which  determine  the  frequency  of  conveyance  of  an  in- 
fectious disease  by  contagion.  There  are  reasons,  some  of  them  very  obvious, 
why  diseases  in  which  the  infectious  substances  are  operative  only  when 
received  into  the  digestive  tract,  and  are  discharged  usually  only  with  the 
feces,  are  less  likely  to  be  transmitted  by  immediate  contagion  than  those 
diseases  in  which  the  virus  is  thrown  off  from  the  skin  on  epidermal  scales. 

But  the  field  of  operation  of  direct  contagion  for  these  so-called  miasmatic- 
contagious  diseases  is  at  most  a  restricted  one  and  the  chief  sources  of  infec- 
tion are  outside  of  the  body  from  which  primarily  the  infectious  germs  may 
have  been  derived.  It  is  to  these  external  sources  of  infection,  which 
are  of  such  importance  in  public  hygiene,  that  I  wish  especially  to  direct 
attention. 
39 


570  EXTEKNAL  SOUECES  OE  IXFECTION 

A  full  comprehension  of  the  sources  of  infection  is,  to  be  obtained  only 
by  a  detailed  study  of  the  etiolog}'  of  the  individual  infectious  diseases,  but 
this  is,  of  course,  impossible  within  the  limits  of  an  address.  It  may,  how- 
ever, be  useful  to  present  some  of  the  facts  which  have  a  general  bearing  upon 
the  subject  Let  us  consider,  then,  from  the  point  of  view  of  modern  bacte- 
riological studies,  what  role,  in  harboring  or  transporting  infectious  agents, 
may  be  played  by  those  substances  or  media  with  which  we  necessarily  come 
into  intimate  contact,  such  as  the  air,  the  ground,  the  water  and  our  food. 

It  is  universally  admitted  that  many  infectious  agents  may  be  transported 
by  the  air,  but  the  extent  of  danger  from  this  source  has  often  been  exag- 
gerated. It  is  a  popular  error  to  suppose  that  most  of  the  minute  particles 
of  dust  in  the  air  either  are  or  contain  living  organisms.  The  methods  for 
determining  the  number  and  kind  of  bacteria  and  fungi  in  the  air  are  now 
fairly  satisfactory,  althougli  by  no  mean?  perfect.  These  have  shown  that 
while  the  number  of  living  bacteria  and  fungi  in  the  atmosphere  in  and 
around  human  habitations  cannot  be  considered  small,  still  it  is  greatly 
inferior  to  that  in  the  ground  or  in  most  waters.  Unlike  fungus  .spores, 
bacteria  do  not  seem  to  occur  to  any  extent  in  the  air  as  single  detached 
particles,  which  would  then  necessarily  be  extremely  minute,  but  rather  in 
clumps  or  attached  to  particles  of  dust  of  relatively  large  size.  As  a  result 
in  a  perfectly  quiet  atmosphere  these  comparatively  heavy  particles  which 
contain  bacteria  rapidly  .settle  to  the  ground  or  upon  underlying  objects 
and  are  easily  filtered  out  by  passing  the  air  through  porous  substances  such 
as  cotton  wool  or  sand.  Kain  washes  down  a  large  number  of  bacteria  from 
the  air.  Tiiat  the  air  bacteria  are  derived  from  the  ground  or  objects  upon 
it  is  shown  by  their  total  absence,  as  a  rule,  from  sea  air  at  a  distance  from 
land,  this  distance  naturally  varjnng  with  the  direction  and  strength  of  the 
wind. 

A  fact  of  capital  importance  in  understanding  the  relations  of  bacteria  to 
the  air,  and  one  of  great  significance  for  preventive  medicine,  is  the  impossi- 
bility of  currents  of  air  detacliing  bacteria  from  moist  surfaces.  Substances 
containing  pathogenic  bacteria,  as,  for  instance,  sputum  containing  tubercle 
bacilli  or  excreta  holding  typhoid  bacilli,  cannot,  therefore,  infect  the  air 
unless  the.«'e  substances  first  become  drj'  and  converted  into  a  fine  powder. 
We  are  able  to  understand  why  the  expired  breath  is  free  from  bacteria  and 
cannot  convey  infection,  except  as  little  particles  may  be  mechanically  de- 
tached by  acts  of  coughing,  sneezing  or  hawking.  Those  bacteria,  the  vitality 
of  which  is  rapidly  destroyed  by  complete  desiccation,  such  as  those  of  Asiatic 
cholera,  evidently  are  not  likely  to  be  transported  as  infectious  agents  by 
the  air,  if  we  except  such  occasional  occurrences  as  their  conveyance  for  a 
short  distance  in  spray. 


BEARING  ON  PEEVENTIVE  MEDICINE  571 

The  only  pathogenic  bacteria  which  hitherto  have  been  found  in  the  air 
are  the  pus  organisms,  including  the  streptococcus  found  by  Prudden  in  a 
series  of  cases  of  diphtheria,  and  tubercle  bacilli,  but  no  far  reaching  con- 
clusions can  be  drawn  from  the  failure  to  find  other  infectious  organisms 
when  we  consider  the  imperfection  of  our  methods  and  the  small  number  of 
observations  directed  to  this  point.  The  evidence  in  other  ways  is  conclusive 
that  many  infectious  agents — and  here  the  malarial  germ  should  be  promi- 
nently mentioned — can  be  and  often  are  conveyed  by  the  air.  While  we 
are  inclined  to  restrict  within  narrower  limits  than  has  been  customary  the 
danger  of  infection  through  the  air,  we  must- recognize  that  this  still  remains 
an  important  source  of  infection  for  many  diseases.  All  those,  however, 
who  have  worked  practically  with  the  cultivation  of  microorganisms  have 
come  to  regard  contact  with  infected  substances  as  more  dangerous  than 
exposure  to  the  air,  and  the  same  lesson  may  be  learned  from  the  methods 
which  modem  surgeons  have  found  best  adapted  to  prevent  the  infection  of 
wounds  with  the  cosmopolitan  bacteria  which  cause  suppuration. 

We  are  not,  of  course,  to  suppose  that  infectious  germs  floating  in  the 
form  of  dust  in  the  atmosphere  are  dangerous,  only  from  the  possibility  of 
our  drawing  them  in  with  the  breath.  Such  germs  may  be  deposited  on  sub- 
stances with  which  we  readily  come  into  contact,  or  they  may  fall  on  articles 
of  food  where  they  may  find  conditions  suitable  for  their  reproduction, 
which  cannot  occur  when  they  are  suspended  in  the  air  in  consequence  of  the 
lack  of  moisture. 

From  the  facts  which  have  been  mentioned  concerning  the  relations  of 
bacteria  to  the  air,  what  points  of  view  present  themselves  to  guide  us  in  pre- 
venting infection  through  this  channel?  Surely  something  more  than  that 
tliis  purpose  is  accomplished  simply  by  abolishing  foul  odors. 

Certain  indications  are  so  plain  as  to  need  only  to  be  mentioned  in  this 
connection,  such  as  the  disinfection  and  removal,  as  far  as  possible,  of  all 
infected  substances,  an  indication  wliich  applies  equally  to  all  channels  of 
infection  and  which  it  is  much  easier  to  mention  than  it  is  to  describe  how 
it  shall  be  realized.  But  there  are  two  indications  which  apply  especially  to 
the  prevention  of  the  transportation  of  disease  germs  by  the  air.  One  is 
the  necessity  of  guarding,  so  far  as  practicable,  against  the  dessication,  when 
exposed  to  the  air,  of  substances  which  contain  infectious  germs  not  de- 
stroyed by  drying,  and  another  is  free  ventilation. 

For  no  disease  is  the  importance  of  the  first  of  these  indications  so  evident 
and  so  well  established  as  for  tuberculosis,  the  most  devastating  of  all  infec- 
tious diseases.  Against  this  disease,  formidable  as  it  may  seem  to  cope  with 
it,  the  courageous  crusade  of  preventive  medicine  has  beg-un  and  is  destined 
to  continue. 


572  EXTERNAL  SOURCES  OF  INFECTION 

It  is  now  generally  recognized  that  the  principal,  although  not  the  sole, 
sources  of  tuberculous  infection  are  the  sputum  of  individuals  affected  with 
pulmonarj'  tuberculosis  and  the  milk  of  tuberculous  cows.  Comet,  who  has 
made  a  laborious  and  most  instructive  experimental  study  of  the  modes  and 
dangers  of  infection  from  tuberculous  sputum,  has  also  elaborated  the 
practical  measures  which  should  be  adopted  to  diminish  or  annihilate  these 
dangers.  These  measures  have  been  so  recently  and  so  widely  published  in 
medical  journals,  and  so  clearly  presented  before  a  section  of  this  association, 
that  I  mention  them  only  to  call  the  attention  of  practitioners  of  medicine 
to  their  importance  and  to  emphasize  the  fact  that  they  are  based  chiefly 
upon  the  principle  that  infectious  substances  of  such  nature  as  tuberculous 
sputum  should  not  be  allowed  to  become  dry  and  converted  into  dust  when 
exposed  to  the  air. 

By  means  of  free  ventilation,  disease-producing  microorganisms  which 
may  be  present  in  the  air  of  rooms  are  carried  away  and  distributed  so  far 
apart  that  the  chance  of  infection  from  this  source  is  removed  or  reduced 
to  a  minimum.  It  is  a  well  established  clinical  observation  that  the  distance 
through  which  the  specific  microbes  of  such  diseases  as  smallpox  or  scarla- 
tina are  likely  to  be  carried  from  the  patient  by  the  air,  in  such  concentration 
as  to  cause  infection,  is  small,  usually  not  more  than  a  few  feet,  but  increases 
by  crowding  of  patients  and  absence  of  free  ventilation.  The  well  known 
experiences  in  the  prophylaxis  and  treatment  of  typhus  fever  are  a  forcible 
illustration  of  the  value  of  free  ventilation. 

It  is,  of  course,  not  to  be  understood  that  by  ventilation  we  accomplish 
the  disinfection  of  a  house  or  apartment.  Ventilation  is  only  an  adjunct  of 
such  disinfection  which,  as  already  mentioned,  is  of  first  importance.  Time 
will  not  permit,  nor  is  it  in  the  plan  of  this  address,  to  discuss  the  details 
of  such  questions  as  house  disinfection,  but  I  may  be  permitted  to  say  that 
the  methods  for  disinfecting  apartments  have  been  worked  out  on  a  satis- 
factory experimental  basis  and  should  be  known,  at  least  by  all  public  health 
officers.  Whether  it  be  pertinent  to  this  occasion  or  not,  I  cannot  forbear  to 
add  my  protest  to  that  of  others  against  placing  reliance  upon  any  method 
hitherto  employed  of  disinfecting  houses  or  apartments  by  fumigation. 
•And  I  would,  furthermore,  call  attention  to  the  lack  in  most  cities  of  this 
country  of  public  disinfecting  establishments  such  as  are  in  use,  with  ex- 
cellent results,  in  many  cities  of  Europe,  and  which  are  indispensable  for 
the  thorough  and  convenient  disinfection  of  clothing,  bedding,  carpets,  cur- 
tains, etc. 

After  this  short  digression  let  us  pass  from  the  consideration  of  the  air 
a.s  a  carrier  of  infection  to  another  important  external  source  of  infection, 
namely,  the  ground.    That  the  prevalence  of  many  infectious  diseases  de- 


BEAEING  0:N'  PEEVENTIVE  MEDICINE  573 

pends  upon  conditions  pertaining  to  the  soil  cannot  be  questioned,  but  the 
nature  and  the  extent  of  this  influence  have  been  and  are  the  subjects  of  lively 
discussion.  The  epidemiological  school,  led  by  Pettenkofer,  assigns,  as  is 
well  known,  to  the  ground  the  chief  and  even  a  specific  and  indispensable 
influence  in  the  spread  of  many  epidemic  diseases,  particularly  cholera  and 
typhoid  fever.  The  statistics,  studies  and  speculations  of  epidemiologists 
which  have  related  to  this  subject  probably  surpass  in  number  and  extent 
those  concerning  any  other  epidemiological  factor.  The  exclusive  ground 
hypothesis  has  become  an  ingenious  and  carefully  elaborated  doctrine  with 
those  who  believe  that  such  diseases  as  cholera  and  typhoid  fever  can  never 
be  transmitted  by  contagion.  These  authorities  cling  to  this  doctrine  with 
a  tenacity  which  indicates  that  on  it  depends  the  survival  of  the  exclusively 
localistic  dogma  of  these  diseases. 

To  all  who  have  not  held  aloof  from  modem  bacteriological  investigations 
it  must  be  clear  that  views  which  have  widely  prevailed  concerning  the  rela- 
tions of  many  infectious  germs  to  the  soil  require  revision.  The  question  is 
still  a  difficult  and  perplexing  one,  but  on  some  hitherto  obscure  or  misunder- 
stood points  these  investigations  have  shed  light,  and  from  the  same  source 
we  may  expect  further  important  contributions  to  a  comprehension  of  the 
relations  of  the  ground  to  the  development  of  infectious  diseases. 

The  ground,  unlike  the  air,  is  the  resting  or  the  breeding  place  of  a  vast 
number  of  species  of  microorganisms,  including  some  which  are  pathogenic. 
Instead  of  a  few  bacteria  or  fungi  in  a  liter,  as  with  the  air,  we  find  in  most 
specimens  of  earth  thousands  and  often  hundreds  of  thousands  of  micro- 
organisms in  a  cubic  centimeter.  Fraenkel  found  the  virgin  soil  almost  as 
rich  in  bacteria  and  fungi  as  that  around  human  habitations. 

This  vast  richness  in  microorganisms  belongs,  however,  only  to  the  super- 
ficial layers  of  the  earth.  Where  the  ground  has  not  been  greatly  disturbed 
by  human  hands  there  is,  as  a  rule,  about  three  to  five  feet  below  the  surface 
an  abrupt  diminution  in  the  number  of  living  organisms,  and  at  the  depth 
where  the  sub-soil  water  usually  lies,  bacteria  and  fungi  have  nearly  or  en- 
tirely disappeared.  Fraenkel,  who  first  observed  this  sudden  diminution  in 
the  number  of  microorganisms  at  a  certain  level  beneath  the  surface,  explains 
this  singular  fact  by  the  formation  at  tliis  level  of  that  sticky  accumulation 
of  fine  particles  consisting  largely  of  bacteria,  which  forms  the  efficient 
layer  in  large  sand  filters  for  water.  Of  course  the  number  of  bacteria  and 
the  depth  to  which  they  penetrate  will  vary  somewhat  with  the  character, 
especially  the  porosity,  of  the  soil  and  its  treatment,  but  the  important  fact 
that  all,  or  nearly  all,  of  the  bacteria  and  fungi  are  retained  in  the  ground 
above  the  level  of  the  sub-soil  water  will  doubtless  hold  true  for  most  situa- 
tions. 


574  EXTERNAL  SOURCES  OF  INFECTION 

The  conditions  are  not  favorable  for  the  multiplication  of  bacteria  in  the 
depth  of  the  jjround,  as  is  shown  by  the  fact  that  in  specimens  of  earth  brought 
to  tiic  surface  from  a  depth  of  a  few  feet,  the  bacteria  which  are  at  first  pres- 
ent rapidly  multiply.  What  all  of  the  conditions  are  which  prevent  the  re- 
production of  bacteria  in  the  deep  soil  has  not  been  ascertained,  but  the  fact 
necessitates  similar  precautions  in  the  bacteriological  examination  of  the 
soil  as  in  that  of  water. 

We  have  but  meagre  information  as  to  the  kinds  of  bacteria  present  in 
the  ground  in  comparison  with  their  vast  number.  Many  of  those  which 
have  been  isolated  and  studied  in  pure  culture  possess  but  little  interest  for 
us  so  far  as  we  know.  To  some  of  the  microorgtmisms  in  the  soil  appears  to 
be  assigned  the  role  of  reducing  or  of  oxidizing  highly  organized  substances 
to  the  simple  forms  required  for  the  nutrition  of  plants.  We  are  in  the  habit 
of  considering  so  much  the  injurious  bacteria  that  it  is  pleasant  to  contem- 
plate this  beneficent  function  so  essential  to  the  preservation  of  life  on  this 
globe. 

Among  the  pathogenic  bacteria  which  have  their  natural  home  in  the 
soil  the  most  widely  distributed  are  the  bacilli  of  malignant  oedema  and  those 
of  tetanus.  I  have  found  ,some  garden  earth  in  Baltimore  extremely  rich  in 
tetanus  bacilli,  so  that  the  inoculation  of  animals  in  the  laboratory  with 
small  bits  of  this  earth  rarely  fails  to  produce  tetanus.  In  infected  localities 
the  anthrax  bacillus  and,  in  two  instances,  the  typhoid  bacillus,  so  far  as  it 
was  possil)le  to  identify  it,  have  been  discovered  in  the  earth.  There  is 
reason  to  believe  that  other  germs  infectious  to  human  beings  may  have 
their  abiding  place  in  the  ground ;  certainly  no  one  doubts  that  the  malarial 
perm  lives  there.  As  the  malarial  germ  has  been  shown  to  be  an  organism 
entirely  ditferent  from  the  bacteria  and  the  fungi,  we  cannot  apply  directly 
to  its  behavior  in  the  soil  and  its  transportation  by  the  air,  facts  which  have 
been  ascertained  only  for  the  latter  .species  of  microorganisms,  and  the 
same  precautions  must  be  observed  for  other  diseases  with  whose  agents  of 
infection  we  are  not  acquainted,  as,  for  instance,  yellow  fever. 

In  view  of  tlie  facility  with  wliich  infectious  germs  derived  from  human 
beings  or  animals  may  gain  ata-ess  to  the  soil,  it  becomes  a  matter  of  great 
importance  to  determine  how  far  such  germs  find  in  the  soil  conditions 
fav()ral)h'  for  thoir  ])rcsorvation  or  their  growth.  We  have,  as  is  well  known, 
a  nunilicr  of  ('j)i(l<'inioh)gi(al  observations  bearing  upon  this  subject,  but 
with  few  exceptions  these  can  be  variously  interpreted  and  it  is  not  my 
puq)ose  to  discuss  them.  The  more  exact  bactc^riological  methods  can,  of 
course,  be  applied  only  to  the  comparatively  small  number  of  infectious  dis- 
eases, the  causative  germs  of  which  have  been  isolated  and  cultivated,  and 
those  methods  liitherto  have  been  applied  to  this  question  oidy  imperfectly. 


BEAEING  ON  PEEVENTIVE  MEDICINE  575 

We  cannot  regard  the  soil  as  a  definite  and  unvarying  substance  in  its 
chemical,  physical  and  biological  properties.  What  has  been  found  true  of 
one  kind  of  soil  may  not  be  so  of  another.  Moreover,  we  cannot  in  our  ex- 
periments bring  together  all  of  the  conditions  in  nature  which  may  have  a 
bearing  on  the  behavior  of  specific  microorganisms  in  the  soil.  W^e  must, 
therefore,  be  cautious  in  coming  to  positive  conclusions  on  this  point  on  the 
basis  of  experiments,  especially  those  with  negative  result.  With  these 
cautions  kept  constantly  in  mind  the  question,  however,  is  one  eminently 
open  to  experimental  .study. 

The  experiments  which  have  thus  far  been  made  to  determine  the  behavior 
of  infectious  microorganisms  in  the  ground  have  related  especially  to  the 
bacilli  of  anthrax,  of  typhoid  fever  and  of  cholera,  and  fortunately  these  are 
the  diseases  about  whose  relations  to  the  ground  there  has  been  the  most 
discussion  and  concerning  which  we  are  most  eager  to  acquire  definite  in- 
formation. 

As  regards  anthrax  bacilli,  it  has  been  determined  that  in  ordinary  garden 
or  field  earth  they  do  not  multiply,  but  in  earth  contaminated  by  blood, 
urine  or  feces  their  reproduction  can  occur.  They  can  grow  on  various 
vegetable  substrata.  There  is  no  reason  to  doubt,  therefore,  that  the  anthrax 
bacilli  can  find  in  or  on  the  ground  suitable  conditions  for  their  multiplica- 
tion, although  such  conditions  are  not  everywhere  present.  For  durable 
infection  of  the  soil  with  anthrax  bacilli,  it  is,  however,  more  important  that 
these  bacilli  should  find  there  suitable  conditions  for  the  formation  of  spores, 
than  that  they  should  be  able  simply  to  multiply.  The  vegetative  forms  of 
anthrax  bacilli  would  not,  as  a  rule,  be  able  to  survive  for  a  great  length  of 
time  the  hostile  influences  which  they  are  likely  to  encounter  in  the  ground, 
such  as  insufficient  or  exhausted  moisture  and  the  attacks  of  saprophytic 
organisms.  On  the  other  hand,  against  these  injurious  influences  the  anthrax 
spores  have  great  resistance.  In  the  superficial  layers  of  the  ground  the 
anthrax  bacilli  may  often  find  those  conditions  of  moisture,  of  temperature, 
of  oxygen  supply  and  of  insufiicient  food,  which  we  know  are  most  favorable 
for  the  development  of  their  spores ;  indeed  Soyka  has  shown  that  the  ground 
presents  often  these  conditions  better  than  our  culture  media.  A  circum- 
stance discovered  by  Feltz,  which,  however,  needs  confirmation,  is,  if  true, 
of  not  little  significance.  He  finds  that  anthrax  bacilli  may  undergo  a  pro- 
gressive diminution  in  virulence  in  the  soil.  If  this  should  be  true  likewise 
of  other  infectious  microorganisms,  we  should  be  able  to  account  in  some 
instances  for  the  variable  degree  of  virulence  which  clinical  observation  in- 
dicates that  certain  agents  of  infection  acquire. 

So  far  as  anthrax  bacilli  are  concerned,  we  may  conclude,  therefore,  that 
the  ground  occasionally  offers  suitable  conditions  for  their  reproduction. 


576  EXTERNAL  SOURCES  OF  INFECTION 

but  what  is  of  greater  importance,  it  offers  especially  favorable  conditions 
for  their  long  continued  preservation  in  the  form  of  spores.  I  must  forego 
here  the  further  consideration  of  the  special  circumstances  inherent  in  the 
soil  which  control  the  origin  and  spread  of  epidemics  of  anthrax  in  cattle, 
although  many  interesting  investigations  have  been  directed  to  this  subject. 

Of  greater  interest  to  physicians  is  the  behavior  of  typhoid  and  of  cholera 
bacteria  in  the  ground.  As  has  already  been  intimated  the  ground  is  re- 
garded by  Pettenkofer  and  his  school  as  the  principal  breeding  place  of  these 
microorganisms  outside  the  body.  This  view,  however,  is  not  supported  by 
bacteriological  investigations.  Inasmuch  as  the  cholera  and  typhoid  bacilli 
may  multiply  on  various  vegetable  substrata  and  substances  derived  from 
animals  at  temperatures  often  present  in  the  ground,  it  is  evident  that  here 
and  there  conditions  may  be  present  for  their  growth  in  the  ground,  but  this 
growth  is  likely  to  be  soon  interrupted  by  the  invasion  of  ordinary  saprophy- 
tic organisms  and  other  harmful  influences.  The  typhoid  bacilli  are  more 
hardy  in  resisting  these  invaders  than  are  the  cholera  bacteria,  which  easily 
succimib,  but  even  for  the  former,  so  far  as  our  present  knowledge  extends, 
the  ground  can  rarely  serve  as  a  favorable  breeding  place. 

It  is  not,  however,  necessary  that  these  organisms  should  multiply  in 
order  to  infect  for  a  considerable  time  the  ground;  it  is  sufficient  if  their 
vitality  is  preserved.  As  to  this  latter  point,  the  reports  of  different  investi- 
gators are  not  altogether  concordant.  Such  excellent  observers  as  Koch, 
Kitasato  and  Uffelmann  found  that  the  cholera  bacteria,  when  added  to  feces 
or  a  mixture  of  feces  and  urine,  rapidly  diminished  in  number  and  at  the 
end  of  three  or  four  days  at  the  most,  had  wholly  disappeared.  In  a  mixture 
of  the  intestinal  contents  from  a  cholera  corpse  with  earth  and  water  Koch 
found  many  cholera  bacteria  at  the  end  of  three  days,  but  none  at  the  end  of 
five  day«.  On  the  other  hand,  G ruber  reports  the  detection  of  cholera  bacteria 
in  dejecta  fifteen  days  old.  The  weight  of  bacteriological  evidence,  there- 
fore, is  opposed  to  the  supposition  that  the  bacteria  of  Asiatic  cholera  pre- 
serve their  vitality  for  any  considerable  time  in  the  ground  or  in  the  excreta. 

With  respect  to  the  bacilli  which  cause  typhoid  fever,  it  has  been  shown 
by  UlTelmann  tliat  tliese  may  live  in  feces,  mixture  of  feces  and  urine,  and 
mixture  of  garden  earth,  feces  and  urine  for  at  least  four  or  five  months, 
and  doubtless  longer,  although  they  may  die  at  the  end  of  a  shorter  period. 
He  also  finds  that  under  these  apparently  unfavorable  conditions  some 
multiplication  of  the  bacilli  may  occur,  although  not  to  any  considerable 
extent.  Grancher  and  Deschamps  found  that  typhoid  bacilli  may  live  in 
the  soil  for  at  least  five  months  and  a  half.  Unlike  the  cholera  bacteria, 
therefore,  the  typhoid  bacilli  may  exist  for  months  at  least  in  the  ground 
and  in  fecal  matter,  holding  their  own  against  the  growth  of  multitudes  of 


BEAEING  ON  PEEVENTIVE  MEDICINE  577 

saprophytes.  This  difference  in  the  behavior  of  cholera  and  of  typhoid 
germs  is  in  harmony  with  clinical  experience. 

As  regards  other  infectious  bacteria  than  those  which  have  been  considered 
I  shall  only  mention  that  tubercle  bacilli,  although  incapable  of  multiplica- 
tion under  the  ordinary  conditions  of  nature  outside  of  the  body,  may  pre- 
serve their  vitality  for  a  long  period  in  the  ground,  on  account  of  their 
resistant  character,  and,  furthermore,  that  the  pyogenic  cocci,  on  account 
of  their  considerably  resistant  nature  and  their  modest  demands  in  the  way 
of  nutriment,  can  be  preserved  and  sometimes  probably  grow  in  the  ground. 
Indeed  Staphylococcus  pyogenes  aureus  has  been  found  in  the  earth  by 
Liibbert. 

The  conclusion  which  we  may  draw  from  the  observations  mentioned  is 
that,  in  general,  the  soil  is  not  a  good  breeding  place  for  most  of  the  infec- 
tious bacteria  with  which  we  are  acquainted,  but  that  it  can  retain  for  a  long 
time  with  unimpaired  vitality  those  which  produce  ispores  or  which  offer 
considerable  resistance  to  injurious  agencies,  such  as  anthrax  bacilli,  typhoid 
bacilli,  tubercle  bacilli  and  the  pyogenic  cocci. 

In  order  to  become  infected  with  bacteria  in  or  on  the  ground,  these  bacteria 
must  in  some  way  be  introduced  into  the  body  and  we  must,  therefore,  now 
attempt  to  determine  how  bacteria  may  be  transported  to  us  from  the  ground. 
So  various  and  intricate  are  the  possibilities  for  this  transportation  that  it 
is  hopeless  to  attempt  to  specify  them  all. 

There  occurs  to  us  first  the  possibility  of  the  conveyance  of  infectious 
microorganisms  from  the  soil  by  means  of  currents  of  air,  a  mode  of  carrying 
infection  which  has  already  been  considered.  Here  I  shall  only  repeat  that 
the  wind  can  remore  bacteria  from  the  ground  only  when  the  surface  is  dry 
and  presents  particles  of  dust,  and  that  the  sole,  and  perhaps  the  chief,  danger 
is  not  that  we  may  inhale  the  infected  dust. 

Manifold  are  the  ways  in  which  we  may  be  brought  into  contact  with  in- 
fectious bacteria  in  the  ground,  either  directly  or  by  means  of  vegetables  to 
which  particles  of  earth  are  attached,  by  the  intervention  of  domestic 
animals,  by  the  medium  of  flies  or  other  insects,  and  in  a  variety  of  other 
ways,  more  or  less  apparent. 

An  important,  doubtless  for  some  diseases  the  most  important,  medium 
of  transportation  of  bacteria  from  an  infected  soil  is  the  water  which  we 
drink  or  use  for  domestic  purposes.  From  what  has  been  said  it  is  evidently 
not  the  sub-soil  water  which  is  dangerous,  for  infections  like  other  bacteria 
cannot  generally  reach  this  in  a  living  state,  but  the  danger  is  from  the 
surface  water  and  from  that  which  trickles  through  the  upper  layers  of  the 
ground,  as  well  as  from  that  which  escapes  from  defective  drains,  gutters, 
eess-pools,  privy  vaults  and  wrongly  constructed  sewers  or  improper  dis- 


578  EXTERNAL  SOURCES  OF  INFECTION 

posal  of  sewerage.  I  shall  have  something  to  say  presently  of  water  as  a 
source  of  infection,  and  shall  not  further  elaborate  here  the  dangers  of  in- 
fection of  drinking  water  through  contaminated  soil,  dangers  which,  especi- 
ally as  regards  typhoid  fever,  are  widely  appreciated  in  this  country,  even  if 
often  imperfectly  counteracted. 

A  point  which  has  been  much  discussed  and  one  of  interest  is,  whether 
bacteria  which  are  in  the  depth  of  the  ground  can  come  to  the  surface.  Two 
agencies  especially  have  been  considered  by  some  as  capable  of  transporting 
bacteria  from  the  depth  to  the  surface.  One  is  ascending  currents  of  air  in 
the  ground  and  the  other  is  the  capillarity  of  fluids  in  the  minute  pores  of 
the  ground.  The  first  of  these  suspected  agencies  must  be  unquestionably 
rejected  in  view  of  the  fact  that  even  a  few  inches  of  sand  is  sufficient  to 
filter  all  of  the  bacteria  out  of  the  air,  even  when  it  is  in  much  more  rapid 
motion  than  can  occur  within  the  ground.  Moreover,  that  degree  of  dryness 
which  is  essential  for  the  detachment  of  bacteria  by  air-currents  is  not 
likely  to  be  present  much  below  the  surface  of  the  ground.  The  experiments 
which  have  been  made  to  determine  to  what  extent  bacteria  may  be  carried 
upward  by  the  capillarity  of  fluids  in  the  ground  have  not  yielded  harmo- 
nious results,  but  the  weight  of  evidence  is  opposed  to  the  belief  that  this  is  a 
factor  of  any  considerable  importance  for  this  purpose. 

From  what  has  been  said  concerning  the  growth  of  pathogenic  bacteria  in 
the  soil  we  shall  not  be  inclined  to  attribute  to  the  multiplication  and  the 
motility  of  these  organisms  much  influence  in  changing  their  places  in  the 
ground. 

Tbe  somewhat  sensational  role  assigned  by  Pasteur  to  earthworms  of 
bringing  bacteria  to  the  surface  cannot  be  wholly  ignored  and  has  received 
support  from  observations  of  Bollinger  regarding  anthrax,  but  it  is  question- 
able whether  much  im})ortance  is  to  be  attached  to  this  agency. 

Regarding  the  depth  to  which  typhoid  bacilli  may  penetrate  in  the  soil, 
the  experiments  of  Grancher  and  Deschamps  shows  that  at  the  end  of  five 
weeks  they  may  reach  a  depth  of  16  to  20  inches  below  the  surface.  As  Hoff- 
mann has  demonstrated  the  extraordinary  slowness  with  which  fluids  and 
fine  ])articles  penetrate  the  soil,  it  Is  probable  that  in  the  course  of  time  a 
greater  depth  than  this  may  be  reached.  Indeed,  Mace  claims  to  have  found 
in  the  neighborhood  of  a  well  suspected  of  infection,  typhoid  bacilli,  to- 
gether witli  ordinary  intestinal  bacteria,  at  a  depth  of  at  least  6^  feet  below 
the  surface.  There  are  a  number  of  instances  recorded  in  which  there  is 
good  reason  to  believe  that  turning  up  the  soil  and  cleaning  out  privies  or 
dung-heaps  in  which  ty}>hoid  stools  have  been  thrown,  have  given  rise  to 
typhoid  fever,  even  after  the  infectious  excreta  have  remained  there  a  year 
or  more. 


BEAEING  ON  PREVENTIVE  MEDICINE  579 

It  cannot  be  said  that  bacteriological  investigations  have  as  yet  shed  much 
light  upon  a  factor  which  plays  a  great  role  in  epidemiology,  namely,  pre- 
disposition to  infection  from  the  ground,  according  to  locality  and  time,  and 
this  deficiency  receives  constant  and  vehement  emphasis  from  the  localistic 
school  of  epidemiologists.  We  can,  however,  readily  understand  that  varying 
conditions,  such  as  temperature,  moisture,  porosity,  quality  of  soil,  may 
exert  a  controlling  influence  in  determining  the  behavior  of  infectious 
germs  in  the  soil  and  the  facility  of  their  transportation  to  human  beings  or 
animals.  As  regards  that  much-discussed  question,  the  significance  of  varia- 
tions in  the  height  of  the  sub-soil  water,  in  relation  to  the  prevalence  of 
certain  epidemic  diseases,  particularly  cholera  and  typhoid  fever,  we  now 
know  that  this  cannot  depend  upon  the  presence  of  bacteria  in  the  sub-soil 
water  itself  or  in  the  capillary  layers  immediately  above  it.  It  has  been 
plausibly  suggested  that  with  the  sinking  of  the  sub-soil  water  fluids  from 
infected  cess-pools,  privy  vaults,  and  other  localities  may  more  readily  be 
drawn  into  wells  or  other  sources  of  water  supply,  and  that  by  the  same 
cause  the  surface  of  the  ground  becomes  dry  so  that  dust  particles  may  be 
lifted  by  the  wind.  Other  more  or  less  plausible  explanations  have  also 
been  offered,  but  it  must  be  confessed  that  our  positive  information  on  the 
point  is  meagre.  There  can,  however,  be  little  doubt  that  this  significance 
of  the  variations  in  sub-soil  water  is  apparent  only  for  certain  localities  and 
has  been  considerably  exaggerated  and  often  misunderstood.  It  is  not, 
however,  pertinent  to  my  theme  to  discuss  this  or  other  purely  epidemiological 
observations  concerning  the  relations  of  the  ground  to  the  spread  of  epidemic 
diseases,  interesting  and  important  as  are  many  of  these  observations. 

Before  leaving  the  subject  of  the  ground  as  a  source  of  infection,  permit 
me  to  indicate  briefly  some  conclusions  which  may  be  drawn  from  what  has 
been  said  as  to  the  principles  which  should  guide  us  in  preventing  infection 
directly  or  indirectly  from  the  ground. 

First  in  importance  is  to  keep  infectious  substances  so  far  as  possible  from 
the  ground.  This  implies  the  early  disinfection  or  de'struction  of  such  sub- 
stances as  typhoid  and  cholera  excreta  and  tuberculous  .sputum. 

Second.  The  ground  should  be  rendered  so  far  as  practicable  unsuitable 
for  the  continued  existence  of  infected  germs.  This,  at  least  for  some  dis- 
eases, is  accomplished  by  a  proper  system  of  drainage,  which,  moreover,  for 
other  reasons  possesses  hygienic  importance. 

Third.  Means  should  be  provided  to  prevent  waste  products  from  getting 
into  the  ground  around  human  habitations  or  from  gaining  access  to  water 
used  for  drinking  or  domestic  purposes.  In  cities  this  can  be  accomplished 
only  by  a  properly  constructed  system  of  sewers.  The  system  of  storing 
waste  products  in  cess-pools  whence  they  are  to  be  occasionally  removed 


580  EXTERNAL  SOURCES  OF  INFECTION 

cannot  be  approved  on  hygienic  grounds.  There  are  conditions  in  which 
the  disposal  of  waste  products  in  deep  wells  only  used  for  this  purpose  and 
whence  these  products  can  filter  into  the  deep  layers  of  the  ground  may  be 
permissible,  but  this  can  never  be  considered  an  ideal  method  of  getting  rid 
of  excrenientitious  substances,  and  is  wholly  wrong  in  regions  where  wells 
are  used  for  drinking  water.  But  I  am  trespassing  with  these  remarks  upon 
a  province  which  does  not  belong  to  me,  but  rather  to  practical  sanitarians 
and  engineers.  I  shall  only  add  that  the  advantage  gained  by  preventing 
organic  waste  from  soaking  into  the  ground  is  not  so  much  that  the  ground 
is  thereby  rendered  better  adapted  for  the  existence  of  infectious  micro- 
organisms, but  is  due  rather  to  the  fact  that  this  waste  is  likely  to  contain 
infectious  germs. 

Finally,  in  cities,  good  pavements,  absence  of  unnecessary  disturbance  of 
the  soil,  cleanliness  of  the  streets,  and  laying  of  dust  by  sprinkling  are  not 
only  conducive  to  comfort,  but  are  sometimes  hygienically  important  in  pre- 
venting infection  from  the  ground  and  dust. 

In  passing  from  the  consideration  of  the  ground  to  that  of  water,  one 
feels  that  he  now  has  to  do  with  a  possible  source  of  infection  against  which 
in  this  country  and  in  England  he  is  at  liberty  to  make  any  accusation  he 
chooses  without  fear  of  contradiction.  There  is  reason  to  believe  that  such 
accusation  has  been  repeatedly  made  without  any  proof  of  misdemeanor  on 
the  part  of  the  water.  It  is  not,  therefore,  with  any  desire  to  awaken  further 
the  medical  or  the  public  conscience  that  I  wish  to  say  a  few  words  concern- 
ing the  beliavior  of  bacteria  in  water  and  the  dangers  of  infection  from  this 
source.  That  such  dangers  are  very  real  must  be  apparent  when  we  consider 
the  universal  employment  of  water  and  its  exposure  to  contamination  from 
all  kinds  of  sources. 

Ordinary  water,  as  is  well  known,  contains  bacteria  in  large  number.  Not 
a  few  species  of  bacteria  can  multiply  rapidly  and  to  a  large  amount  even 
in  di.stilled  water.  These  are  the  so-called  water-bacteria,  and  like  most  of 
the  microorganisms  found  in  ordinary  drinking  water  are  perfectly  harmless 
saprophytes.  What  we  wish  to  know  is,  how  pathogenic  microorganisms 
conduct  themselves  in  water.  Can  they  grow  or  be  preserved  for  any  length 
of  time  in  a  living  condition  in  water?  As  regards  the  multiplication  of 
pathogenic  bacteria  in  water  the  results  of  different  experimenters  do  not 
altogether  agree,  ^\^le^cas  Bolton  failed  to  find  any  gro\vi;h,  but  rather  a 
progressive  diminution  in  the  number  of  pathogenic  bacteria  planted  in 
sterilized  water.  Wolffhiigol  and  Ricdel  observed  a  limited  reproduction  of 
such  bacteria,  including  those  of  typhoid  fever  and  cholera.  This  difference 
is  due,  probably,  to  the  methods  of  experimentation  employed.  According 
to  Kraus,  tlicse  latter  bacteria  diminish  rapidly  in  number  in  unsterilized 


BEARING  ON  PREVENTIVE  MEDICINE  581 

spring  or  well  water  kept  at  a  low  temperature.  These  experiments  indicate 
that  water,  even  when  contaminated  with  more  organic  impurities  than  are 
likely  ever  to  be  present  in  drinking  water,  is  not  a  favorable  breeding  place 
for  pathogenic  bacteria.  Still  it  is  to  be  remembered  that  these  laboratory- 
experiments  do  not  reproduce  exactly  all  of  the  conditions  in  nature,  and  it 
may  happen  that  in  some  nook  or  cranny  or  vegetable  deposit  at  the  side  of 
a  well  or  stream  some  pathogenic  bacteria  may  find  suitable  conditions  for 
their  multiplication. 

But  as  has  been  repeatedly  emphasized  in  this  address  it  is  not  necessary 
that  pathogenic  bacteria  should  actually  multiply  in  a  medium  in  order  to 
render  it  infectious.  It  is  sufficient  if  their  life  and  virulence  are  not  de- 
stroyed in  a  very  short  time.  As  to  this  important  point  Bolton  found  that 
in  sterilized  water  typhoid  bacilli  may  preserve  their  vitality  for  over  three 
months  and  cholera  bacteria  for  8  to  14  days,  while  Wolffhiigel  and  Riedel 
preserved  the  latter  in  water  for  about  80  days.  Under  natural  conditions, 
however,  these  organisms  are  exposed  to  the  over  growth  of  the  water 
bacteria  so  that  Kraus  found  in  unsterilized  water  kept  at  a  temperature  of 
10.5°  C.  (50.9°F.)  the  typhoid  bacilli  no  longer  demonstrable  after  7  days, 
and  the  cholera  bacteria  after  2  days.  The  conditions  in  Kraus's  experiments 
were  as  unfavorable  as  possible  for  the  continued  existence  of  these  patho- 
genic bacteria,  more  unfavorable  than  those  often  present  at  the  season  of 
prevalence  of  cholera  and  typhoid  fever,  nevertheless  I  do  not  see  that  they 
justify  the  conclusions  of  Kraus  as  to  the  slight  probability  of  drinking 
water  ever  conveying  infection  with  the  germs  of  typhoid  fever  and  cholera. 
To  render  such  a  conclusion  probable  it  would  be  necessary  to  demonstrate 
a  much  shorter  preservation  than  even  Kraus  himself  found.  In  judging 
this  question  it  should  not  be  overlooked  that  infection  of  drinking  water 
with  the  typhoid  or  the  cholera  germs  is  not  so  often  the  result  of  throwing 
typhoid  or  cholera  stools  directly  into  the  source  of  water  supply  as  it  is  the 
consequence  of  leaky  drains,  cess-pools,  privy-vaults  or  infected  soil,  so  that 
there  may  be  continued  or  repeated  accessions  of  infected  material  to  the 
water. 

In  view  of  the  facts  presented,  there  is  no  sufficient  reason,  therefore,  from 
a  bacteriological  point  of  view,  of  rejecting  the  transmissibility  of  typhoid 
fever  and  cholera  by  the  medium  of  the  drinking  water.  This  conclusion 
seems  irresistible  when  we  call  to  mind  that  Koch  once  found  the  cholera 
bacteria  in  large  number  in  the  water  of  a  tank  in  India,  and  that  the  typhoid 
bacilli  have  been  repeatedly  found  in  drinking  water  of  localities  where 
typhoid  fever  existed.  Nor  do  I  see  how  it  is  possible  to  interpret  certain 
epidemiological  facts  in  any  other  way  than  by  assuming  that  these  diseases 
can  be  contracted  from  infected  drinking  water,  although  I  know  that  there 


582  EXTERNAL  SOURCES  OF  INFECTION 

are  still  higli  authorities  who  obstinately  refuse  to  accept  this  interpretation 
of  the  facts. 

In  this  connection  it  may  be  mentioned  that  pathogenic  bacteria  may 
preserve  their  vitality  longer  in  ice  than  in  unsterilized  drinking  water. 
Thus  Prudden  found  typhoid  bacilli  still  alive  which  had  been  contained 
in  ice  for  103  days. 

When  we  come  to  consider  the  ways  in  which  water  may  become  infected 
with  pathogenic  microorganisms  we  recognize  at  once  a  distinction  in  this 
respect  between  surface  water  and  sub-soil  water.  Whereas  the  sub-soil 
water  may  be  regarded  under  ordinary  circumstances  and  in  most  places  as 
germ-free,  the  surface  water,  such  as  that  in  rivers,  and  streams,  is  exposed 
to  all  manner  of  infection  from  tlie  ground,  the  air,  and  the  admission  of 
waste  substances.  Unfortunately  in  the  ordinary  way  of  obtaining  sub-soil 
water  for  drinking  purposes  by  means  of  dug  wells  this  distinction  is  obliter- 
ated, for  the  water  which  enters  these  wells  free  from  bacteria  is  converted 
into  a  surface  water  often  exposed,  by  the  situation  of  the  well,  to  more 
dangerous  contamination  than  other  surface  waters  used  for  drinking  pur- 
poses. 

Now  let  us  turn  our  attention  as  we  have  done  with  other  sources  of  in- 
fection to  a  brief  outline  of  certain  general  principles  which  may  help  us  in 
avoiding  infection  from  the  water. 

We  shall  in  the  first  place  avoid  so  far  as  possible  the  water  suspected  of 
infection,  especially  with  the  germs  of  such  disease  as  typhoid  fever  and 
cholera.    When  it  is  necessary  to  use  this  suspected  water  it  should  be  boiled. 

As  regards  the  vital  question  of  water  supply,  it  may  be  stated  as  a  general 
principle  that  no  hygienic  guarantee  can  be  given  for  the  purity  of  surface 
water  which  has  not  been  subjected  to  a  proper  system  of  filtration,  or  for 
the  purity  of  spring  or  well  water  fed  from  the  sub-soil  unless  such  water  is 
protected  from  the  possibility  of  infection  through  the  upper  layers  of  the 
soil  or  from  the  air.  This  is  not  saying  that  water  which  meets  certain 
cliemical  and  ])i()logioal  tests  and  which  is  so  situated  that  the  opportunities 
for  its  contamination  appear  to  be  absent  or  reduced  to  a  minimum  is  not 
admissible  for  the  supply  of  drinking  water,  but  the  possibility  of  infection 
can  bo  removed  only  by  the  fulfillment  of  the  condition  named,  and  upon 
these  conditions  the  hygienic  purist  will  always  insist. 

Unfortunately  we  have  at  present  no  domestic  filters  which  are  satisfactory 
and  most  of  the.«e  in  common  use  are  worse  than  none,  as  they  soon  furnish 
a  filtrate  richer  in  bacteria  than  the  original  water.  The  only  effective 
method  of  water-filtration  for  the  general  supply  is  by  means  of  large  sand 
filters  such  as  arc  in  use  with  excellent  results  in  Berlin  and  some  other 
cities.    These  require  skilled  attention.     I  cannot  on  this  occasion  discuss 


BEAEING  ON  PREVENTIVE  MEDICINE  583 

the  construction  or  working  of  these  filters  but  would  refer  those  who  are 
interested  to  the  full  and  careful  investigations  of  the  Berlin  filters  by 
Wolffhiigel  and  by  Plagge  and  Proskauer. 

What  is  accomplished  by  these  artificial  sand  filters  is  accomplished  under 
natural  conditions,  also  by  the  ground,  which  furnishes  a  sub-soil  water  free 
from  microorganisms,  and  to  obtain  pure  water  we  have  only  to  devise  means 
by  which  this  sub-soil  water  may  be  secured  without  the  chance  of  contamina- 
tion. Just  as  the  water,  which  has  passed  through  the  sand  filters,  is  col- 
lected in  suitable  reservoirs  and  is  distributed  in  pipes,  which  do  not  admit 
contamination  from  without,  so  by  means  of  properly  constructed  artesian 
or  driven  wells  we  may  secure  the  naturally  filtered  sub-soil  water  with  the 
same  freedom  from  the  chances  of  infection. 

It  is  well  to  bear  in  mind  that  no  biological  or  chemical  tests  of  water  can 
replace  those  measures  which  have  been  mentioned  as  necessary  to  secure 
purity  of  water  supply.  These  tests  are  of  value  only  when  applied  with 
proper  precautions  and  with  due  consideration  of  the  special  circumstances 
of  each  case  for  which  they  are  employed.  There  has  been  much  profitless 
discussion  as  to  whether  greater  significance  is  to  be  attached  to  the  chemical 
or  to  the  bacteriological  examination  of  water.  Each  has  its  own  special 
field  of  application  and  in  this  the  one  cannot  replace  the  other  method. 
The  bacteriological  examination  has  for  hygienic  purposes  the  specific  agents 
of  infection  in  the  form  of  microorganisms,  as  has  already  been  done  for 
cholera  bacteria  and  typhoid  bacilli,  but  this  is  a  comparatively  rare  result 
and  does  not  at  present  afford  a  wide  field  of  application  for  this  method. 
The  significance  of  the  bacteriological  test  is  to  be  based  more  frequently 
upon  the  fact  that  it  concerns  itself  with  the  same  class  of  microorganisms 
to  which  some  of  the  recognized  and  doubtless  many  of  the  undiscovered  in- 
fectious agents  belong  and  from  the  behavior  of  which  in  some  respects  con- 
clusions can  be  drawn  as  to  the  behavior  of  the  pathogenic  organisms.  Thus 
the  bacteriological  test  is  the  only  one  which  enables  us  to  judge  correctly 
of  the  efficacy  of  those  methods  of  filtration  of  surface  water  and  of  con- 
struction of  wells  which  insure  purity  of  water  supply.  The  points  of  view 
from  which  we  can  estimate  correctly  according  to  our  present  knowledge 
the  relative  merits  and  fields  of  application  of  the  chemical  and  of  the  bacte- 
riological methods  of  water  examination  have  been  clearly  indicated  by 
Plagge  and  Proskauer  and  by  Wolffhiigel.  The  theme  is  one  beyond  the 
limits  or  the  scope  of  this  discourse  and  I  have  referred  to  its  chiefly  to  em- 
phasize the  fact  that  we  cannot  rely  upon  chemical  or  bacteriological  tests  of 
water  to  the  exclusion  of  those  protective  measures  which  have  been  men- 
tioned, although  I  do  not  intend  to  imply  that  each  of  these  tests  when 
properly  employed  does  not  afford  important  information  and  is  not  of  great 
value  in  many  cases. 


584  EXTERNAL  SOURCES  OF  INFECTION 

I  have  already  taxed  so  largely  your  time  and  patience  that  I  must  pass 
over  with  brief  mention  the  food  as  a  source  of  infection.  Unlike  those 
external  sources  of  infection  which  we  have  hitherto  considered,  many 
articles  of  food  afford  an  excellent  nutritive  medium  for  the  growth  of  a 
number  of  species  of  pathogenic  microorganisms,  and  in  many  instances 
this  growth  may  be  abundant  without  appreciable  change  in  the  appearance 
or  taste  of  the  food. 

When  we  consider  in  how  large  degree  the  certainty  and  the  severity  of 
infection  with  many  kinds  of  pathogenic  microorganisms  depend  upon  the 
number  of  such  organisms  received  into  the  body,  we  can  appreciate  that 
the  danger  of  infection  from  food  which  contains  a  mass  of  growing  patho- 
genic bacteria  may  be  much  greater  than  that  resulting  from  the  reception 
of  infected  water  or  air,  media  in  which  infected  organisms  are  rarely 
present  in  other  than  a  very  dilute  condition.  The  entrance  into  the  body 
of  a  single  infectious  bacterium  with  the  inspired  air  is,  at  least  in  the 
case  of  many,  many  diseases,  not  likely  to  cause  infection,  but  let  this 
bacterium  fall  upon  some  article  of  food,  as  for  instance  milk,  where  it 
can  multiply  in  a  short  time  at  a  favorable  temperature  many  thousand 
fold,  and  evidently  the  chances  of  infection  become  vastly  increased. 

Among  the  various  agencies  by  which  infectious  organisms  may  gain 
access  to  the  food  may  be  mentioned  the  deposition  of  dust  conveyed  by 
the  air,  earth  adhering  to  vegetables,  water  used  in  mixing  with  or  in  the 
preparation  of  food,  in  cleaning  dishes,  clothes,  etc.,  and  contact  in  mani- 
fold other  ways  with  infected  substances. 

Fortunately  a  very  large  part  of  our  food  is  sterilized  in  the  process  of 
cooking  shortly  before  it  is  partaken,  so  that  the  danger  of  infection  from 
this  source  is  greatly  diminished  and  comes  into  consideration  only  for  un- 
cooked or  partly  cooked  food  and  for  food,  which,  although  it  may  have  been 
thoroughly  sterilized,  is  allowed  to  stand  considerable  time  before  it  is  used. 
I\Iilk,  in  consequence  of  its  extensive  use  in  an  unsterilized  state  and  of  the 
excellent  nutritive  conditions  which  it  presents  to  many  pathogenic  bacteria, 
should  be  emphasized  as  especially  liable  to  convey  certain  kinds  of  infection, 
a  fact  supported  not  less  by  bacteriological  than  by  clinical  observations. 
Ilesse  found  that  also  a  large  number  of  ordinary  articles  of  food  prepared 
in  the  kitchen  in  the  usual  way  for  the  table  and  then  sterilized  afford  a 
good  medium  for  the  growth  and  preservation  of  typhoid  and  cholera 
bacteria,  frequently  without  appreciable  change  in  the  appearance  of  the 
food. 

Upon  solid  articles  of  food  bacteria  may  multiply  in  separate  colonies,  so 
that  it  may  readily  happen  that  only  one  or  two  of  those  who  partake  of  the 
food  eat  the  infected  part,  whereas  with  infected  liquids,  such  as  milk,  the 


BEARING  ON"  PREVENTIVE  MEDICINE  585 

infection  is  more  likely  to  be  transmitted  to  a  larger  number  of  those  who  are 
exposed. 

In  another  important  particular  the  food  differs  from  the  other  sources 
of  infection  which  we  have  considered.  Not  only  the  growth  of  infectious 
bacteria,  but  also  that  of  bacteria  incapable  of  multiplication  within  the 
body,  may  give  rise  in  milk  and  other  kinds  of  food  to  various  ptomaines, 
products  of  fermentation  and  other  injurious  substances  which  when  ingested 
are  hkely  to  cause  more  or  less  severe  intoxication  or  to  render  the  alimentary 
tract  more  susceptible  to  the  invasion  and  multiplication  of  genuinely  in- 
fectious organisms. 

It  is  plain  that  the  liability  to  infection  from  food  will  vary  according  to 
locality  and  season.  In  some  places  and  among  some  races  the  proportion  of 
uncooked  food  used  is  much  greater  than  in  other  places  and  among  other 
races.  In  general,  in  summer  and  in  autumn,  the  quantity  of  fruit  and  food 
ingested  in  the  raw  state  is  greater  than  at  other  seasons,  and  during  the 
summer  and  autumn  there  is  also  greater  danger  from  the  transportation 
of  disease  germs  from  the  ground  in  the  form  of  dust  and  the  amount  of 
liquids  imbibed  is  greater.  The  elements  of  predisposition,  according  to 
place  and  time  upon  which  epidemiologists  are  so  fond  of  laying  stress,  are 
not,  therefore,  absent  from  the  source  of  infection  now  under  consideration. 

I  have  thus  far  spoken  only  of  the  secondary  infection  of  food  by  patho- 
genic microorganisms,  but,  as  is  well  known,  the  .substances  used  for  food 
may  be  primarily  infected.  Chief  in  importance  in  the  latter  category  are 
the  various  entozoa  and  other  parasites  which  infest  animals  slaughtered  for 
food.  The  dangers  to  mankind  resulting  from  the  diseases  of  animals  form 
a  separate  theme,  which  would  require  more  time  and  space  than  this  address 
affords  for  their  proper  consideration.  I  shall  content  myself  on  this  occasion 
with  only  a  brief  reference  to  infection  from  the  milk  and  flesh  of  tuberculous 
cattle. 

It  has  been  abundantly  demonstrated  by  numerous  experiments  that  the 
milk  from  tuberculous  cows  is  capable  when  ingested  of  causing  tubercu- 
losis. How  serious  is  the  danger  may  be  seen  from  the  statistics  of  Bollinger 
who  found  with  cows  affected  with  extensive  tuberculosis  the  milk  infectious 
in  80  per  cent  of  the  cases,  in  cows  with  moderate  tuberculosis  the  milk  in- 
fectious in  66  per  cent  of  the  cases  and  in  cows  with  slight  tuberculosis  the 
milk  infectious  in  33  per  cent  of  the  cases.  Dilution  of  the  infected  milk 
with  other  milk  or  with  water,  diminished  or  in  sufficient  degree  it  removed 
the  danger  of  infection.  From  statistics  furnished  me  by  Mr.  A.  W.  Clement, 
V.  S.,  it  appears  that  the  number  of  tuberculous  cows  in  Baltimore  which  are 
slaughtered  is  not  less  than  3  to  4  per  cent.  Among  some  breeds  of  cattle 
tuberculosis  is  known  to  be  much  more  prevalent  than  this. 
40 


586  EXTERNAL  SOURCES  OF  INFECTION" 

There  is  no  evidence  that  the  meat  of  tuberculous  cattle  contains  tubercle 
bacilli  in  suiEcient  number  to  convey  infection,  unless  it  be  very  exceptionally. 
Nevertheless  one  will  not  willingly  consume  meat  from  an  animal  known  to 
be  tuberculous.  This  instructive  repugnance,  as  well  as  the  possibility 
of  postmortem  infection  of  the  meat  with  tubercle  bacilli  in  dressing  the 
animal  seem  good  grounds  for  discarding  such  meat.  The  question,  however 
as  to  the  rejection  of  meat  of  tuberculous  animals  has  important  economic 
bearings  and  has  not  been  entirely  settled.  As  to  the  rejection  of  the  milk 
from  such  animals,  however,  there  can  be  no  difference  of  opinion,  although 
this  is  a  point  not  easily  controlled. 

The  practical  measure  to  adopt  in  order  to  avoid  infection  from  the  food 
are  for  the  most  part  sufficiently  obvious.  Still  it  is  not  to  be  expected  that 
every  possibility  of  infection  from  this  source  will  be  avoided.  It  is  difficult 
to  discuss  the  matters  considered  in  this  address  without  seeming  to  pose  as 
an  alarmist.  But  it  is  the  superficial  and  the  half  knowledge  of  these  subjects 
which  is  most  likely  to  exaggerate  the  dangers.  While  one  will  not  under 
ordinary  circumstances  refrain  from  eating  raw  fruit  or  food  which  has  not 
been  thoroughly  sterilized  or  from  using  unboiled  or  natural  waters  in  the 
fear  that  he  may  swallow  typhoid  or  cholera  bacteria,  still  in  a  locality  in- 
fected with  cholera  typhoid  fever  he  will,  if  wise,  not  allow  himself  the  same 
freedom  in  these  respects.  Cow's  milk,  unless  its  source  can  be  carefully 
controlled,  should  when  used  as  an  habitual  article  of  diet  as  with  infants, 
be  boiled  or  the  mixed  milk  of  a  number  of  cows  should  be  selected,  but  this 
latter  measure  offers  less  protection  than  the  former. 

In  most  places  in  this  country  we  are  sadly  lacking  in  good  sanitary  in- 
spection of  the  food,  especially  of  the  animal  food,  offered  for  sale.  One 
cannot  visit  the  slaughter  house  in  Berlin  or  in  Munich,  and  doubtless 
similar  ones  are  to  be  found  elsewhere,  and  watch  the  intelligent  and  skilled 
inspection  of  the  slaughtered  animals  without  being  impressed  with  our 
deficiency  in  this  respect.  In  large  cities  an  essential  condition  for  the 
efficient  sanitary  inspection  of  animal  food  is  that  there  should  be  only  a 
few  places,  and  preferably  only  one  place,  where  animals  are  permitted  to 
be  slaughtered.  Skilled  veterinarians  should  be  selected  for  much  of  the 
work   of   inspection. 

It  may  reasonably  be  asked  that  the  national  government  which  has  already 
spent  so  much  money  for  the  extermination  of  such  diseases  as  pleuro- 
pneumonia and  hog  cholera,  which  arc  not  known  to  endanger  the  health  of 
mankind,  should  turn  its  attention  also  to  means  for  eradicating  tuberculosis 
from  cattle,  which  is  scourge  not  only  to  the  economic  interests  of  farmers 
and  dairymen,  but  also  to  the  health  of  human  beings. 


BEAEING  ON  PREVENTIVE  MEDICINE  587 

Without  any  pretension  to  having  done  more  in  this  address  than  to  sketch 
here  and  there  a  few  principles  derived  from  bacteriological  researches  con- 
cerning only  some  of  the  most  widely  distributed  external  sources  of  in- 
fection, I  trust  that  enough  has  been  said  to  show  the  folly  of  any  exclusive 
dogma  as  to  modes  of  infection.  The  ways  of  infection,  even  in  one  and 
the  same  disease,  are  manifold  and  various,  and  can  never  be  resolved  into 
exclusive  hypothesis,  such  as  the  drinking  water  hypothesis,  the  ground 
hypothesis,  etc. 

It  follows,  therefore,  that  it  is  not  by  sanitary  improvements  in  one  direc- 
tion only  that  we  can  control  the  spread  of  preventable  epidemic  diseases. 
In  one  situation  improvements  in  the  supply  of  drinking  water  check  the 
prevalence  of  typhoid  fever,  in  another  place  similar  measures  show  no  such 
influence ;  or,  again,  in  one  city  the  introduction  of  a  good  system  of  sewer- 
age diminishes  epidemic  diseases,  and  in  another  no  similar  result  follows. 
We  should,  therefore,  aim  to  secure  so  far  as  possible  good  sanitary  arrange- 
ments in  all  directions  and  in  all  respects. 

It  has  also  been  rendered  evident  in  what  has  been  said  that  infectious 
agents  differ  markedly  from  each  other  in  their  behavior,  so  that  while  public 
sanitation  aims  at  those  measures  which  are  found  to  be  most  widely  bene- 
ficial, it  should  not  forget  that  each  infectious  disease  is  as  much  a  separate 
problem  in  its  prophylaxis  as  in  its  symptomatology,  etiology  and  treatment. 
It  will  not  aim  to  combat  cholera  with  the  means  found  best  adapted  to 
scarlet  fever,  but  it  will  adapt  preventive  measures  as  directly  to  the  specific 
end  in  view  as  possible. 

In  presenting  to  you  the  results  of  researches,  chiefly  bacteriological,  con- 
cerning the  scientific  basis  of  preventive  medicine,  I  hope  to  escape  the 
accusation  of  one-sidedness  and  narrowness  by  the  statement  that  I  do  not  for 
a  moment  intend  to  imply  that  the  bacteriological  method  is  our  only  source 
of  accurate  knowledge  on  the  subjects  which  have  been  considered.  My  aim 
is  accomplished  if  I  have  succeeded  in  making  clear  that  this  method  has 
established  facts  which  aid  in  a  clearer  conception  of  the  causes  of  some  im- 
portant infectious  diseases,  in  a  better  understanding  of  the  sources  and 
dangers  of  infection,  and  in  a  more  efficient  selection  and  application  of 
sanitary  measures. 

/  If  this  science  of  only  a  few  years'  growth  has  furnished  already  acquisi- 
tions to  knowledge  so  important,  so  far  reaching,  toay  we  not  look  forward 
with  assurance  to  the  solution  of  many  dark  problems  in  the  domain  of  in- 
fectious diseases,  problems  the  solution  of  which  may  yield  to  preventive 
medicine  a  future  of  usefulness  and  success  which  we  cannot  now  foresee. 


SANITATION  IN  RELATION  TO  THE  POOR' 

The  sanitary  condition  of  the  poor  is  a  matter  which  concerns  not  the  poor 
alone,  hut  the  whole  community.  There  is  abundant  evidence  to  show  that 
the  health  of  a  city  is  influenced  in  a  large  measure  by  the  condition  of  the 
abodes,  the  habits  and  the  surroundings  of  the  poor.  The  removal,  so  far 
as  practicable,  of  unsanitary  conditions  attendant  upon  poverty  is  not  a 
philanthropic  undertaking  only,  but  it  is  a  duty  which  states  and  cities  owe 
to  all  of  the  citizens. 

There  are  several  reasons  why  it  seems  proper  and  desirable  to  bring  before 
this  Charity  Organization  Society  a  question  which  is  so  largely  one  of  the 
state  and  municipal  policy. 

The  charity  organizations  of  this  country  have  become  one  of  the  powerful 
agencies  for  influencing  and  directing  public  sentiment,  and  consequently 
civic  action,  in  such  matters  as  public  sanitation. 

These  organizations,  moreover,  are  interested,  not  only  in  the  immediate 
alleviation  of  distress  due  to  poverty,  but  also  in  searching  after  the  under- 
lying conditions  and  in  basing  remedial  measures  so  far  as  possible  upon 
these  conditions.  There  can  be  no  complete  study,  no  adequate  solution,  of 
the  social  question  without  a  knowledge  of  the  influence  of  unhygienic  con- 
ditions upon  the  physical,  mental  and  moral  state  of  the  poor,  as  well  as 
of  the  effect  of  poverty  in  producing  these  conditions. 

A.  third  reason  why  it  is  desirable  to  introduce  this  subject  here,  is  that 
it  is  in  the  power  of  individuals  doing  the  work  of  this  organization  to  diffuse 
some  sanitary  knowledge  among  the  poor.  The  results  of  such  individual 
effort  may  not  be  great  as  compared  witli  what  may  and  should  be  done  by 
public  agencies,  but  they  will  do  some  good,  especially  in  the  direction  of 
domestic  hygiene,  a  subject  of  which  women  can  be  excellent  tcacliers. 

Sanitation  among  the  poor  in  this  threefold  relation  to  public  hygiene,  to 
the  social  problem  and  to  the  individual  work  of  tliis  organization  is  of 
course  a  theme  far  beyond  the  limits  assigned  to  me  upon  this  occasion.  I 
shall  be  able  to  touch  upon  only  a  few  of  the  salient  points. 

The  two  circumstances  which  have  had  the  most  potent  influence  in  the 
development  of  modem  sanitary  science  have  been  the  occurrence  of  great 
epidemics  of  disease,  especially  of  cholera,  and  also  in  this  country  of  yellow 

*  An  address  delivered  before  tlie  Charity  Organization  Society  of  Baltimore, 
November  14,  1892. 
Bait.,  1892,  14  p.,  8". 
588 


SANITATION  IN  RELATION  TO  THE  POOR  589 

fever,  and  the  belief  in  the  dependence  of  those  diseases  usually  called 
zymotic  or  infectious  upon  filth. 

If  the  public  cannot  be  awakened  in  any  other  way  to  the  correction  of 
glaring  sanitary  defects  than  by  an  outbreak  of  cholera,  then  such  a  visitation 
is  not  an  unmixed  evil,  for  in  a  few  years  more  lives  will  probably  be  saved 
by  the  removal  of  well  known  causes  of  preventable  disease  than  are  destroyed 
by  the  cholera,  and  the  chances  of  a  renewal  of  the  epidemic  will  be  les,sened, 
if  not  wholly  abolished. 

Hamburg  has  been  warned  time  and  again  by  sanitarians  of  the  danger 
of  using  unfiltered  Elbe  water  for  drinking  purposes,  but  it  has  required  the 
sacrifice  within  the  space  of  a  few  weeks  of  eight  thousand  lives  and  untold 
misery  for  this  warning  to  be  heeded. 

It  is  fortunate  that  public  sanitary  measures  have  been  controlled  so 
largely  by  the  belief  that  most  infectious  diseases  depend  upon  filth.  In 
this  belief  the  main  purpose  of  public  sanitary  efforts  has  been  to  render  pure 
the  water  we  drink,  the  air  we  breath,  the  food  we  eat  and  the  soil  upon 
which  we  live. 

Within  the  last  dozen  years  we  have  acquired  definite  knowledge  of  the 
causes  of  some  of  the  most  important  infectious  diseases  and  we  now  know 
that  these  diseases  are  not  generated  by  filth  in  so  direct  a  manner  as  was 
once  supposed.  We  may  drink  contaminated  water,  breath  impure  air  and 
live  on  a  polluted  soil  without  getting  typhoid  or  typhus  fever,  or  diphtheria 
or  scarlet  fever  or  other  infectious  disease.  These  influences  may  be  and 
doubtless  are  deleterious  to  health,  but  unless  the  specific  germs  of  disease 
have  been  introduced,  they  do  not  produce  well  defined  diseases. 

Many  of  these  disease  germs,  however,  are  widely  distributed  and  there 
is  good  reason  to  believe  that  such  unhygienic  conditions  as  those  mentioned 
afford  to  many  the  best  opportunities  for  multiplication  and  for  conveyance 
to  the  human  body. 

If  we  render  difficult  or  impossible  the  contamination  of  our  water,  air, 
food  and  soil,  with  ordinary  impurities  which  may  not  in  themselves  be 
demonstrably  harmful,  we  make  difficult  or  impossible  their  contamination 
with  the  germs  of  many  diseases. 

We  are  thus  enabled  to  understand  how  there  may  be  serious  sanitary 
defects  in  a  place  vdthout  such  an  injurious  influence  upon  health  as  to 
attract  much  attention.  Nevertheless,  these  defects  are  a  constant  menace 
to  the  health  of  the  inhabitants.  The  demonstration  of  sewage  contamination 
in  the  sources  of  supply  of  drinking  water  is  significant,  not  because  the  ad- 
mixture with  sewage  is  in  itself  dangerous,  but  because  it  indicates  that  the 
gates  are  open  for  the  entrance  into  the  water  of  the  germs  of  typhoid  fever 
or  of  cholera,  if  these  germs  are  present  in  the  sewage.    It  is  true  that  cholera. 


590  SANITATION  IN  RELATION  TO  THE  POOR 

for  instance,  might  be  introduced  into  such  a  place  and  by  a  fortunate  chance 
the  germs  of  the  disease  not  gain  entrance  to  the  soil  or  to  the  water  so  as  to 
produce  an  epidemic,  but  is  it  not  foolish  and  short  sighted  to  leave  the 
lives  and  happiness  of  thousands  dependent  upon  such  a  chance  when  we 
know  what  measures  are  necessary  in  order  to  reduce  the  chance  to  a  mini- 
mum, if  not  to  eliminate  it  altogether?  The  most  ordinary  prudence  de- 
mands that  the  open  gates  be  closed.  One  of  the  most  instructive  lessons  of 
the  visitations  of  Asiatic  cholera  in  Europe  since  1884  has  been  the  failure 
of  this  disease  to  gain  a  foot-hold  when  introduced  into  cities  with  irreproach- 
able water  supply  and  sewage  disposal. 

That  there  are  serious  sanitary  defects  in  Baltimore,  is  well  known. 
Attention  has  been  called  repeatedly  to  most  of  them  by  the  health  officers 
of  the  city  and  by  others.  The  annual  reports  of  the  health  department  have 
for  many  years  recommended  the  abolition  of  the  present  primitive  methods 
of  disposal  of  excreta  and  house-wastes.  Dr.  Robe  in  his  report  for  1890 
says :  "  It  is  impossible  to  find  language  capable  of  expressing  in  its  entirety 
the  filthiness  and  dangers  to  life  and  health  by  which  we  are  surrounded  so 
long  as  the  present  privy  system  is  maintained,"  and  Dr.  McShane,  the 
present  Commissioner  of  Health  endorses  these  views  and  says :  "  Nothing 
of  greater  importance  can  be  suggested  than  the  adoption  of  some  means  for 
the  proper  removal  and  disposal  of  household  and  other  sewage." 

The  present  health  commissioner  and  others  have  recently  called  public 
attention  to  serious  sewage  contamination  of  the  sources  of  water  supply  of 
Lake  Roland,  which  affords  drinking  water  to  a  large  part  of  the  city. 

Notwithstanding  these  notorious  violations  of  .sanitary  principles,  this 
city  appears  to  be  reasonably  healthy.  Indeed  during  the  latter  half  of  the 
decade  1880-90  the  death  rate  of  Baltimore  as  officially  given  out,  reached  a 
point  which  has  been  regarded  as  the  ideal  of  perfection  for  modern  cities, 
so  that  the  mayor  in  his  message  in  1887  claimed  for  Baltimore  "  a  lower  rate 
of  mortality  than  prevails  in  any  city  in  Europe  or  America."  I  deem  it, 
however,  proper  to  say,  that  during  tliis  decade  the  official  death  rate  was 
computed  upon  the  basis  of  a  gross  exaggeration  of  the  population,  and  was 
therefore  smaller  than  the  true  death  rate.  At  the  beginning  of  the  decade, 
in  the  Report  of  the  Health  Department  for  1880,  the  estimated  population 
was  61,483  in  excess  of  the  U.  S.  Census  for  the  census  year  1879-80,  and  at 
the  end  of  the  decade  in  1888  and  1889  the  estimated  population  was  65,904 
in  excess  of  the  U.  S.  Census  for  1890  and  44,916  in  excess  of  the  police  census 
for  1890.  In  accounting  for  the  apparently  great  increase  in  the  death  rate 
in  1890  as  compared  with  1889 — an  increase  from  17.4  per  1000  in  1889  to 
22.41  in  1890 — the  commissioner  of  health  in  his  report  for  1890  says, 
"  Inasmuch  as  the  estimated  population  on  which  the  calculation  of  the 


SA^ITATIO^  IN  EELATIOX  TO  THE  POOR  591 

mortality  rate  was  based  was  nearly  50,000  too  high,  the  increase  in  the  death 
rate  is  only  partly  an  actual  increase." 

In  calling  attention  to  the  serious  errors  in  the  official  death  rates  of  this 
city  during  the  period  mentioned,  I  would  not  be  understood  as  basing 
the  plea  for  sanitary  reforms  upon  an  alarming  mortality  in  this  city.  While 
there  is  nothing  alarming  in  the  death  rate  of  this  as  compared  with  other 
cities,  I  believe  that  we  have  now  sufficient  experience  as  to  the  beneficial 
effects  of  sanitary  reforms  to  justify  the  prediction  that,  as  regards  infant 
mortality  and  certain  infectious  diseases,  the  mortality  in  this  city  could  be 
materially  reduced  by  the  introduction  of  such  improvements  in  public  sani- 
tation as  belong  to  a  well  managed  modern -city.  The  teaching  of  experience 
is  direct  and  uniform  in  this  regard. 

I  have  already  endeavored  to  point  out  that  serious  sanitary  defects, 
although  for  a  time  they  may  not  appear  to  injure  the  health  of  those  exposed 
to  them,  become  a  standing  menace  to  health  upon  the  approach  of  certain 
epidemic  diseases. 

But  I  do  not  consider  it  necessary  to  base  the  argument  for  sanitary  im- 
provements exclusively  upon  their  demonstrable  influence  on  public  health, 
manifest  as  their  influence  often  is.  Such  things  as  pure  drinking  water, 
well  paved  and  clean  streets,  and  well  drained  soil  are  conducive  to  comfort 
and  happiness  and  to  the  commercial  welfare  of  a  city.  They  exert  in  this 
way  a  direct  influence  upon  prosperity  and  an  indirect  influence  upon  health, 
not  appreciable  by  any  mortality  statistics,  but  clear  enough  to  the  experience 
of  individuals  and  of  the  community. 

This  matter  of  pubHc  sanitation  is  one  purely  of  municipal  administra- 
tion. I  suppose  that  those  who  have  the  power  to  initiate  and  carry  out 
measures  necessary  to  secure  to  us  a  water  supply  free  from  danger  of  con- 
tamination, a  civilized  system  of  disposal  of  sewage,  weU  paved  and  clean 
streets,  good  drainage,  freedom  from  pollution  of  our  water  courses  and 
harbor,  removal  of  dwellings  which  cannot  be  made  fit  for  human  habitation, 
conceive  that  their  personal  and  political  interests  lie  in  quite  different 
directions,  and  for  this  indifference  the  apathy  of  the  general  public  is  largely 
responsible. 

Eecommendations  of  health  officials,  reports  of  special  commissions,  ad- 
dresses to  tax  payers'  associations,  are  unheeded. 

Great  as  are  the  cost  and  the  practical  difficulties  in  executing  municipal 
engineering  works,  they  have  been  successfully  surmounted  by  cities  less 
favorably  placed  as  to  natural  advantages  and  pecuniary  resources  than  is 
this  city. 

Mr.  Andrew  D.  White  makes  a  strong  statement  when  he  says  that,  "  With- 
out the  slightest  exaggeration  we  may  assert  that,  with  a  few  exceptions,  the 


593  SANITATION  IN  EELATION  TO  THE  POOR 

city  governments  in  the  United  States  are  the  worst  in  Christendom,  the 
most  expensive,  the  most  inefficient  and  the  most  corrupt,"  but  so  high  an 
authority  in  sanitary  matters  as  Dr.  John  S.  Billings  says  that  this  state- 
ment "  is  true  ,so  far  as  municipal  engineering  work  is  concerned  with  regard 
to  several  of  the  largest  cities  in  this  country."  I  cannot  forbear  from  quot- 
ing in  this  connection  a  passage  from  Mr.  Joseph  Chamberlain's  article  in 
the  last  number  of  the  "  Forum  "  on  "  Municipal  Institutions  in  America 
and  England."  After  showing  that  the  expenditures  for  local  purposes  in 
the  city  of  Boston  are  largely  in  excess  of  those  in  the  City  of  Birmingham, 
England,  he  says :  "  The  leading  idea  of  the  English  system  may  be  said  to 
be  that  of  a  joint  stock  or  cooperative  enterprise  in  which  every  citizen  is  a 
shareholder  and  of  which  the  dividends  are  receivable  in  the  improved  health 
and  the  increase  in  the  comfort  and  happiness  of  the  community.  The 
members  of  the  council  are  the  directors  in  this  great  business,  and  their  fees 
consist  in  the  confidence  and  the  gratitude  of  those  among  whom  they  live. 
In  no  other  undertaking  whether  philanthropic  or  commercial,  are  the  re- 
turns more  speedy,  more  manifest  or  more  beneficial.  To  give  a  .single  illus- 
tration the  reforms  in  Birmingham  carried  out  in  a  few  years  reduced  the 
death  rate  from  26.8  per  1000  in  1874  to  19  in  1888.  In  other  words  the 
initiation  of  the  unpaid  members  of  the  council  and  their  supervision  of 
the  loyal  and  assiduous  labors  of  the  paid  officials  have  been  the  means  of 
saving  the  lives  of  more  than  3000  persons  in  a  single  year ;  and  inasmuch 
as  for  a  single  death  many  cases  of  illness  not  actually  fatal  may  be  reckoned, 
it  is  easy  to  see  what  a  mass  of  human  suffering  has  been  lightened  and  how 
much  misery  has  been  prevented," 

In  view  of  Mr.  Chamberlain's  description  of  municipal  administration  in 
Birmingham  it  is  interesting  to  note  that  tlie  Special  Commission  appointed 
in  1889  by  Mayor  Davidson  to  examine  all  the  departments  of  the  city 
government  of  Baltimore  and  to  make  such  recommendations  as  they  deem 
appropriate,  recommended  the  appointment  of  unpaid  commissions  of  citi- 
zens to  be  at  the  head  of  several  departments  of  the  city  government,  such  as 
the  Board  of  Health,  the  Board  of  Public  Works  and  the  Board  of  City 
Charities. 

It  has  seemed  to  me  necessary  to  say- at  least  these  few  words  regarding 
the  relation  of  public  health  to  municipal  government,  in  order  that  we  may 
be  under  no  illusion  as  to  what  can  be  accomplished  for  sanitary  reform  in 
the  condition  of  the  poor  outside  of  public  agencies.  I  realize  fully  that  what 
is  needed  in  this  matter  is  active  work.  Interested  observers  and  critics  we 
have  in  abundance,  but  the  active  workers  for  reform  are  few.  Our  dis- 
satisfaction with  the  intruments  at  our  disposal  should  of  course  make  us 
try  to  get  better  ones,  but  in  the  meantime  we  can  accomplish  much  with 
those  which  we  already  have,  and  it  is  the  part  of  practical  wisdom  to  take 


SANITATION  IN  RELATION  TO  THE  POOR  593 

hold  of  these  instruments  and  apply  them  to  the  best  use  possible  under  the 
circumstances.  Our  health  officials  are  often  well  aware  of  the  vices  of  the 
system  under  wliich  they  are  obliged  to  work  and  I  believe  that  they  will 
welcome  any  cooperation  and  assistance  which  public  spirited  citizens  and 
organizations  are  able  to  render  them.  Under  our  existing  political  condi- 
tions, experience  seems  to  show  that  more  can  be  accomplished  by  the  quiet, 
intelligent  and  well  directed  efforts  of  individuals  and  of  such  organizations 
as  societies  for  city  improvement,  which  do  not  directly  antagonize  those 
who  wield  political  power,  and  which  receive  the  approval  of  the  general 
public,  than  by  spasmodic  political  movements  for  reform. 

Of  the  problems  more  directly  relating  to  sanitation  among  the  poor  in 
its  bearing  upon  public  health,  the  medical  relief  of  the  poor  is  the  most 
amply,  even  if  not  the  most  judiciously,  provided  for.  The  medical  treat- 
ment of  the  poor  is  to  a  very  large  extent  gratuitously  assumed  by  the  medi- 
cal profession.  In  this  respect  physicians  perform  an  amount  of  impaid 
labor  without  any  parallel  in  other  professions  or  business.  So  great  are 
the  abuses  of  medical  charities  that  these  have  been  described  as  the  greatest 
pauperizing  agency  now  in  existence.  This  subject  has  been  so  often  dis- 
cussed and  has  been  so  frequently  presented  before  Charity  Organization 
Societies,  that  I  shall  not  dwell  upon  it.  Great  benefit  has  been  derived 
from  the  cooperation  in  isome  cities  of  Charity  Organization  Societies  in 
investigating  the  circumstance  of  patients  applying  for  gratuitous  medical 
relief  in  hospitals  and  dispensaries,  and  a  more  extended  and  perfect  system 
of  such  cooperation  might  be  usefully  inaugurated  in  this  city. 

There  is  one  need  which  is  iSO  urgent  in  this  city  that  public  attention 
should  be  forcibly  directed  to  it  and  that  is  a  hospital  for  infectious  diseases. 
Dr.  Robe,  when  he  was  commissioner  of  health,  in  1890  urgently  recom- 
mended the  construction  of  such  a  hospital,  and  his  successor  has  em- 
phatically endorsed  this  recommendation.  At  present  no  hospital  in  the  city 
will  undertake  to  receive  cases  of  scarlet  fever,  diphtheria  or  smallpox. 
When  one  considers  the  necessity  of  prompt  isolation  of  these  cases  in  order 
to  prevent  their  epidemic  distribution  and  of  our  helplessness  in  this  regard  in 
the  emergency  of  a  visitation  of  cholera  or  yellow  fever,  it  is  clear  that  this 
is  a  matter  which  should  receive  immediate  attention. 

A  public  establishment  for  disinfecting  by  .steam  is  scarcely  less  important 
and  is  now  provided  in  most  large  cities  which  can  lay  any  claim  to  decent 
sanitation.  Among  the  most  important  results  of  the  discovery  and  study 
of  the  specific  germs  which  cause  infectious  diseases,  has  been  the  develop- 
ment of  the  methods  necessary  to  destroy  these  germs  outside  of  the  body 
when  their  presence  is  suspected  in  such  substances  as  clothing,  bed  linen, 
household  furniture,  etc.  Some  methods  of  disinfection  which  were  formerly 
and  are  still  sometimes  relied  upon,  are  now  known  to  be  inefficacious. 


594  SAI^ITATION  IN  EELATION"  TO  THE  POOR 

There  is  now  universal  agreement  of  opinion  that  heat  is  the  most  powerful 
and  useful  disinfectant  agent.  Every  large  city  should  be  supplied  with  a 
public  establishment  for  disinfecting  by  steam,  with  which  it  would  be  well 
to  combine  a  crematory  for  burning  articles  which  cannot  be  disinfected  or 
are  not  worth  disinfecting.  The  disinfection  of  rooms,  furniture,  bedding, 
etc.,  should  be  intrusted  to  a  corps  of  men  who  are  trained  for  the  purpose. 

The  housing  of  the  poor  is  a  sanitary  problem  which  offers  the  greatest 
difficulties,  but  there  are  few  sanitary  questions  which  have  received  more 
intelligent  discussion  and  treatment  from  philanthropic  and  practical  men 
and  women. 

In  all  efforts  to  benefit  the  poor,  but  especially  here,  we  have  to  distinguish 
two  classes  of  the  poor,  between  which  the  lines  cannot  be  sharply  drawn. 
In  one  class  are  those  who  earn  small  wages,  to  whom  the  struggle  for  exist- 
ence is  hard,  who  manage  to  preserve  decency  and  self-respect,  and  in  the 
other  class  are  the  failures  of  life,  the  criminal,  the  drunkard,  the  tramp  and 
the  loafer  and  also  a  few  who  have  been  temporarily  forced  by  adverse  circum- 
stances to  this  low  level,  but  who  are  capable  of  rising. 

For  the  first  class,  it  seems  to  have  been  demonstrated  that  healthful 
dwellings  can  be  furnished  at  a  price  within  their  ability  to  pay,  and  that 
these  yield  a  fair  return  on  the  investment.  Over  the  construction  of  these 
dwellings  and  tenement  houses,  the  health  officials  should  exercise  a  rigid 
sanitary  supervision  to  insure  their  proper  supply  with  water,  air  and  light 
and  to  control  the  arrangements  for  drainage  and  disposal  of  excreta. 

Of  the  second  class  of  the  very  poor,  Mr.  Theodore  Thomson  in  his  paper 
on  "  The  Housing  of  the  Poorer  Classes,"  read  before  the  Seventh  Inter- 
national Congress  of  Hygiene  and  Demography  in  London  says :  "  Some- 
thing else  will  have  to  be  done  with  the  lowest  class  of  all.  Of  these  it  may 
be  said  that  were  they  to-morrow  housed  in  a  palace,  they  would  in  ten  days 
make  it  a  pig  .sty.  For  them  remedies  are  required  other  than  those  needful 
for  the  class  immediately  above  them.  No  doubt  they  will,  despite  them- 
selves, to  some  extent  be  benefited  by  sanitary  arrangements  in  tlieir  dwell- 
ings, by  demolition  of  unhealthy  areas,  by  improved  lodging  houses  under 
existing  laws.  But  so  long  as  there  is  an  insanitary  building  left,  they  will 
go  to  it,  for  they  do  not  admire  sanitation.  They  will  avoid  all  model  dwell- 
ings for  they  do  not  wish  to  be  cleanly  and  orderly  as  there  prescribed  by 
rule,  and  they  will  destroy  and  fill  with  filth  any  interior  that  becomes  theirs. 
It  is  to  be  hoped  that  the  benefits  of  education  will  effect  some  improvement 
in  the  members  of  this  class,  but  it  must  be  a  long  time  before  these  benefits 
create  any  appreciable  effect.  Private  effort,  such  as  the  noble  work  of  Miss 
Octavia  Hill  and  others,  is  one  of  the  means  to  which  one  may  look  with  hope. 
Possibly  registration  of  the  worst  class  of  houses  with  frequent  and  stringent 
supervision  of  the  habits  of  the  inmates,  may  be  useful.    Such  supervision 


SANITATION  IN  RELATION  TO  THE  POOR  595 

would  not  be  pleasant  to  the  inmates,  but  it  is  perhaps  desirable  that  life 
should  not  be  made  too  pleasant  for  this  class  of  society,  most  of  whom 
deserve  no  sympathy  other  than  that  which  one  bestows  on  the  victims  of 
heredity." 

Mr.  Alfred  White,  who  is  to  speak  to  us  this  evening,  in  his  paper  on  this 
subject  at  the  Conference  of  Charities  and  Corrections  in  1885,  believes  that 
the  class  of  people  who  prefer  squalor  and  darkness  to  decency  and  light, 
who  need  moral  reformation  before  they  can  be  properly  moved  into  better 
surroundings,  is  a  small  minority  of  the  laboring  class  here  as  compared 
with  London. 

Something  must  be  done  for  this  apparently  hopeless  class ;  if  not  for  their 
own  sake,  at  least  for  the  sake  of  the  rest  of  the  community.  If  their  exist- 
ence among  us  is  inevitable,  they  at  any  rate  should  not  be  permitted  to 
occupy  abodes  unfit  for  human  habitation,  which  endanger  the  health  of 
their  neighbors  and  of  the  whole  community  and  which  may  become  the 
breeding  places  of  pestilence.  I  believe  that  such  houses  if  they  cannot  be 
made  decently  healthful,  and  some  cannot,  should  be  demolished.  What  is 
to  become  of  the  inmates  ?  I  reply  that  some  will  move  elsewhere,  and  that 
is  well,  some  will  be  forced  to  lead  more  decent  lives,  and  that  is  also  well, 
and  some  will  go  to  the  almshouse.  It  is  better  and  in  the  long  run  cheaper 
for  the  city  to  take  care  of  this  remnant  in  the  almshouse  than  to  permit  them 
to  live  as  they  now  do. 

Between  1879  and  1890  in  the  city  of  Dublin  2556  unsanitary  houses  have 
been  cleared  of  tenants  and  closed.  More  than  one-half  have  been  completely 
removed  and  the  other  half  have  been  extensively  repaired  and  rendered 
habitable.  This  is  one  of  the  great  sanitary  reforms  which  have  been  carried 
out  in  that  city  by  Sir  Charles  Cameron  during  the  past  twelve  years,  and 
which  have  led  to  the  almost  complete  extinction  of  typhus  fever  and  to 
other  most  gratifying  results  in  the  improvement  of  public  health. 

The  impression  is  a  general  one  that  the  working  classes  are  better  houses 
in  Baltimore  than  in  most  large  eastern  cities,  and  I  think  that  this  is  cor- 
rect. According  to  the  10th  census  (the  returns  of  11th  census  on  this  point 
are  not  yet  available)  the  average  number  of  persons  to  a  dwelling  was  in 
Baltimore  6.54,  in  Philadelphia  5.79,  in  Boston  8.26,  in  Cincinnati  9.11, 
and  in  New  York  16.37.  This  means  that  with  us  the  great  majority  of  the 
families  of  the  working  classes  have  each  a  separate  house.  There  are, 
however,  in  this  city  instances  in  which  several  families  are  crowded  into 
houses  intended  originally  for  a  single  family,  and  this  condition  is  of  course 
worse  than  that  of  a  well  constructed  tenement  house  intended  for  many 
families.  How  common  these  instances  are  is  not  known,  and  it  is  much  to  be 
desired  that  trustworthy  data  should  be  collected  concerning  the  housing  of 
the  poor  in  this  city.    An  important  and  useful  work  might  be  done  if  this 


596  SANITATION  IN  KELATION  TO  THE  POOE 

Charity  Organization  Society,  or  some  other  public  agency,  or  even  some 
individual,  had  the  inclination  and  the  means  to  put  to  work  a  body  of 
volunteer  .sanitary  inspectors  who  should  do  for  this  city  what  a  corps  of 
similar  inspectors  under  Mr.  Dwdght  Porter  has  done  in  the  investigation 
of  tenement  house  districts  in  Boston.  Mr.  Porter  was  assisted  by  certain 
students  from  the  Institute  of  Technolog}-.  They  received  the  hearty  co- 
operation of  the  official  board  of  health. 

The  most  important  means  at  the  disposal  of  departments  of  public  health 
for  the  prevention,  detection  and  removal  of  unsanitary  conditions,  is  a 
body  of  efficient  sanitary  inspectors  acting  under  suitable  sanitary  laws.  In 
some  cities  such  inspection  is  carried  out  with  admirable  system.  It  requires 
intelligence,  tact  and  special  training  on  the  part  of  the  inspectors.  We  are 
sadly  deficient  as  regards  the  inspection  of  slaughter  houses,  animal  food, 
milk  and  dairies.  The  services  of  one  or  more  skilled  veterinarians  are  need- 
ful for  much  of  this  work  and  they  cannot  act  efficiently  without  better  laws 
regulating  these  matters  than  we  now  have.  The  number  of  sanitary  in- 
spectors now  employed  by  our  board  of  health  seems  to  me  too  small  to  per- 
form efficiently  the  work  which  should  be  done. 

We  have  thus  far  considered  the  sanitary  state  of  the  poor  more  especially 
in  its  relation  to  the  rest  of  the  community.  I  hope  that  it  is  apparent  that 
merely  from  a  mercenary  and  commercial  point  of  view  it  is  for  the  interest 
of  the  community  to  take  care  of  tlie  health  of  the  poor.  Philanthropy 
assumes  a  totally  different  aspect  in  the  eyes  of  the  world  when  it  is  able  to 
demonstrate  that  it  pays  to  keep  the  people  healthy.  "  The  health  of  the 
people  is  the  wealth  of  the  state."  This  may  be  a  sordid  and  mercenary  way 
of  looking  at  the  question,  but  it  is  the  way  which  has  enabled  reformers  to 
convince  mankind  of  the  necessity  of  public  sanitary  measures.  It  is  esti- 
mated, and  of  course  such  an  estimate  can  be  only  a  rough  one,  that  nearly 
100,000  deaths  occur  annually  in  this  countr}'  from  preventable  causes. 
For  each  death  there  are  of  course  several  cases  of  illness  not  fatal,  due  to 
preventable  causes.  One  can  form  from  such  a  statement  some  idea  of  the 
enormous  loss  in  money  and  productive  labor  which  we  suffer  from  prevent- 
able causes  of  illness  and  death. 

The  influence  of  unsanitary  conditions  upon  the  health,  the  character  and 
the  morals  of  the  poor  is  manifestly  an  important  question  in  .sociology.  A 
good  deal  has  been  written  upon  it,  but  mostly  in  a  vague  and  indefinite  way. 
The  subject  has  not  received  the  scientific  investigation  which  it  deserves 
and  many  of  the  existing  data  are  untrustworthy. 

The  death  rate  is  stated  to  be  from  two  to  three  times  greater  among  the 
very  poor  than  among  those  better  situated.  But  it  is  not  only  as  to  the 
influence  of  unsanitary  conditions  upon  the  health,  but  upon  the  whole 


SANITATION  IN  RELATION  TO  THE  POOR  597 

physical,  mental  and  moral  constitution  of  those  subjected  to  them,  that  we 
wish  information. 

It  is  of  course  self-evident  that  insufficient  and  wretched  food,  filthy  sur- 
roundings, close  and  impure  air  and  overcrowding  must  effect  not  only  the 
health  but  also  the  habits  and  morals  of  those  subjected  to  such  an  environ- 
ment. Is  any  moral  regeneration  possible  under  such  circumstances?  Is 
not  the  first  step  a  regeneration  of  the  physical  environment  ? 

The  picture  has  l»een  drawn  of  the  man  of  the  alley  who  comes  home  from 
his  work.  After  stumbling  over  the  filthy  refuse  heap  in  front  of  the  house, 
he  enters  a  dingy  and  repulsive  abode  in  which  the  air  is  close  and  depressing. 
The  small  room  is  crowded  and  it  is  pervaded  with  offensive  odors.  The  food 
is  scanty  and  ill  cooked.  Near  by  is  a  capacious  room,  relatively  clean,  where 
conversation  and  excitement  may  be  found,  where  to  him  everything  is  bright 
and  alluring  and  where  for  a  few  coppers  he  can  get  something  which  for  a 
time  stimulates  him  and  makes  him  forget  his  misery.  The  wonder  is  not 
so  much  that  one  man  reels  home  drunk  and  a  brute,  but  that  for  every  such 
one  there  are  not  a  dozen.  It  is  not  difficult  to  comprehend  the  reply  which 
was  made  by  such  a  man  to  the  clerg}'man  who  remonstrated  with  him.  "  If 
you  were  to  come  and  live  and  sleep  here,  you,  sir,  would  drink  whiskey  too." 

The  immorality  which  must  necessarily  ensue  from  bestial  over-crowding 
has  been  depicted  often  enough. 

But  it  is  not  so  much  these  gross  and  flagrant  vices  which  spring  from 
unwholesome  living  that  I  wish  to  emphasize  at  present.  These  are  the 
themes  of  sermons  and  tracts  and  are  well  known.  These  vices  belong  in  a 
large  part  to  a  class  of  the  poor  which  many  believe  to  be  irreclaimable. 

The  class  best  worth  helping  are  the  industrious,  hard-working  wage 
earners,  struggling  to  make  a  decent  living,  who  possess  a  fair  degree  of 
intelligence  and  preserve  their  self-respect. 

Whether  many  of  these  shall  keep  their  heads  above  the  water  or  shall  sink 
to  the  submerged  class,  depends  I  believe  in  larger  measure  upon  their  sani- 
tary surroundings  than  is  generally  supposed.  Many  of  these  worthy  people 
live  under  very  unfavorable  hygienic  conditions  which  can  be  remedied. 
Many  are  ignorant  of  the  simplest  rules  of  health.  They  suffer  often  a 
gradual  physical  deterioration  not  amounting  to  actual  illness.  Their  minds 
and  characters  suffer  with  the  body.  Many  of  these  poor  people  become 
intemperate,  not  usually,  as  many  temperance  reformers  seem  to  think,  be- 
cause they  deliberately  choose  to  be  drunkards,  but  as  a  natural  result  of  the 
circumstances  under  which  they  are  forced  to  live.  It  is  useless  to  appeal  to 
the  self-control  of  these  individuals  and  to  leave  them  breathing  a  polluted 
atmosphere  in  unwholesome  houses  with  scanty  and  bad  food. 

It  has  become  more  and  more  evident  that  the  great  work  of  charity  in 
the  future  is  to  consist,  not  so  much  in  almsgiving,  as  in  efforts  to  educate 


698  SANITATIOI^  IX  EELATION  TO  THE  POOR 

the  poor,  to  strengthen  their  characters,  to  lift  them  up  physically, 
mentally  and  morally.  A  fundamental  part  of  this  uplifting  must  be  an 
improvement  in  the  sanitary  conditions  in  the  abodes  of  the  poor  and  in- 
struction in  domestic  hygiene.  I  have  little  confidence  in  the  remedial 
efficacy  of  measures  wliich  do  not  include  this  fundamental  work. 

I  believe  that  the  workers  in  this  and  similar  organizations  who  visit  the 
houses  of  the  poor,  can  do  much  good  in  carrying  to  them  the  simpler  lessons 
in  domestic  hygiene  as  to  such  matters  as  ventilation,  cooking,  household 
cleanliness,  etc.  They  can  also  make  clear  the  necessity  of  certain  simple 
precautions,  such  as  boiling  the  water  and  the  milk,  to  be  exercised  at  the 
approach  of  certain  epidemic  diseases,  such  as  cholera  and  typhoid  fever. 

This  implies  that  these  workers  themselves  possess  the  requisite  informa- 
tion. Sanitary  science  is  less  of  an  intuitive  nature  than  many  seem  to 
suppose.  Knowledge  of  it  is  to  be  gained  by  reading  good  books  on  the  sub- 
ject, by  demonstrations  and  by  lectures,  and  I  venture  to  suggest  that  it 
might  be  well  for  this  organization  to  make  some  provision  for  its  workers 
in  the  way  of  instruction  in  sanitation.  Although  my  theme  has  been  sani- 
tation among  the  poor,  it  is  not  to  be  understood  that  the  rich  do  not  also 
suffer  their  full  .share  from  sins  of  ignorance  and  neglect  in  matters  of  health. 

In  conclusion  I  would  say  that  in  emphasizing  the  importance  of  sanitary 
reform,  I  do  not  for  a  moment  suppose  that  this  is  the  only  agency  to  be  used 
in  elevating  the  condition  of  the  poor.  There  are  other  motives  to  work  and 
other  agencies  to  be  employed  which  occupy  a  much  loftier  plane  than  those 
which  I  have  treated. 

Still  less  do  I  suppose  that  even  perfect  sanitation  would  be  a  panacea 
for  the  evils  attendant  upon  poverty.  The  roots  of  these  evils  lie  far  beneath 
the  surface.  It  may  be  that  they  are  inseparable  from  existing  conditions  of 
society  and  from  the  present  industrial  system  and  that  nothing  .short  of  a 
social  revolution  can  wholly  remove  them. 

But  we  need  not  wait  for  a  reconstruction  of  society  and  tlie  introduction 
of  some  scheme  which  we  would  now  call  Utopian  in  order  to  bring  relief. 
How  many  generations  will  pass  before  this  radical  relief  will  come,  if  it 
come  at  all,  no  one  can  tell.  Our  present  duty  is  to  make  use  of  the  best 
instrumentalities  available  and  among  those  which  promise  the  surest  and 
quickest  and  happiest  results  is  sanitary  improvement.  I  would  therefore 
earnestly  commend  to  the  attention  of  those  engaged  in  the  great  and  rapidly 
developing  work  of  our  modern  organized  and  associated  charities  the  im- 
portance of  including  in  this  work  efforts  to  improve  the  sanitary  surround- 
ings of  the  poor  and  to  educate  the  poor  in  matters  pertaining  to  healtli. 


ASIATIC  CHOLERA  IN  ITS  RELATIONS  TO  SANITARY 

REFORMS ' 

Since  the  appearance  of  Asiatic  cholera  in  Europe  last  summer,  and 
especially  since  its  arrival  in  the  harbor  of  New  York  last  autumn,  and  its 
persistence  in  Europe  during  the  winter,  an  unusual  degree  of  public  interest 
in  sanitary  matters  has  been  awakened  throughout  this  country.  This  is 
due  mainly  to  the  popular  apprehension  lest  this  most  dreaded  of  epidemic 
diseases  should  gain  a  foot-hold  in  this  country  during  the  coming  summer 
and  autumn. 

Unwonted  attention  is  given  to  public  health  administration.  The 
national  government  provides  additional  legislation  regarding  quarantine. 
There  is  a  general  cry  for  cleaner  streets,  removal  of  public  nuisances,  and 
more  efficient  sanitary  inspection.  The  character  of  the  water  supply  is 
scrutinized.  Measures,  often  more  vigorous  than  wise,  are  taken  to  remedy 
sanitary  defects  of  long  growth.  Hospitals  for  infectious  diseases  and 
modern  disinfecting  plants  are  demanded.  Committees  and  conferences  of 
citizens  and  of  various  civic  organizations  are  formed.  Magazines  and  news- 
papers are  lending  their  aid,  often  most  efficiently,  toward  education  of  the 
public  and  measures  for  improved  sanitation.  The  public  is  readier  to 
listen  than  at  ordinary  times. 

A  similar  awakening  of  public  interest  in  isanitation  has  attended  the 
approach  of  cholera  in  the  past.  However  near  or  remote  one  may  consider 
a  visitation  of  cholera,  whether  or  not  one  may  approve  of  much  which  is 
written  on  this  subject  at  present,  and  of  some  of  the  measures  urged  for 
the  prevention  of  this  disease,  anyone  interested  in  sanitary  improvements 
must  welcome  the  increased  attention  given  to  this  subject  and  the  larger 
opportunity  to  secure  some  permanent  additions  to  our  sanitary  resources. 
This  feeling  may  be  tempered  by  the  fear  that  now  as  in  the  past  excitement 
and  sudden  emergencies  may  lead  to  hasty  and  inconsiderate  measures  and 
foolish  and  wasteful  expenditure  of  money,  but  this  makes  it  all  the  more 
desirable  to  take  advantage  of  the  opportunity  and  to  try  to  direct  thought 
and  action  into  the  right  channels. 

In  this  way  surely  some  good  can  be  done.  Knowledge  of  the  simpler 
principles  of  hygiene  can  be  more  widely  diffused  among  the  people.  The 
sanitary  sense,  even  of  the  more  enlightened,  can  be  further  cultivated.    The 

iPop.  Health  Mag.,  Wash.,  1893-94,  I. 

599 


600  ASIATIC  CHOLERA 

inhabitants  of  cities  may  be  led  to  take  some  active  personal  interest  in  the 
sanitary  condition  of  their  towns.  Sanitary  defects  can  be  brought  into 
clearer  light  and  to  some  extent  remedied.  Public  health  administration  can 
be  aided  and  improved.  Possibly  a  hospital  for  infectious  diseases,  a  public 
disinfecting  establishment,  even  some  important  work  in  municipal  engi- 
neering, improved  methods  of  registration  of  vital  statistics  or  better  sani- 
tary legislation  can  be  secured. 

Some  knowledge  of  the  nature  and  mode  of  distribution  of  infectious  dis- 
eases must  be  useful  to  those  interested  in  questions  of  public  health,  and, 
although  each  infectious  disease  presents  its  own  peculiar  problems  there  is 
none  which  can  teach  more  important  and  helpful  lessons  in  sanitation  than 
cholera,  and  there  is  none  which  has  had  so  profound  an  influence  upon  the 
development  of  modern  hygiene. 

Cholera  is  to  us  of  the  nineteenth  century  the  chief  reminder  of  the  great  7 
pestilences  of  former  centuries  which  have  disappeared  from  civilized  lands.  / 
These  great  pestilences  were  attributed  for  the  most  part  to  causes  beyond 
human  control,  such  as  the  anger  of  an  offended  Deity  or  some  mysterious 
epidemic  constitution  of  the  atmosphere.  The  careful  study  of  the  mode  of 
spread  of  epidemic  cholera  has  given  the  early  impulse  and  chief  support 
to  the  doctrine,  which  is  the  mainspring  of  modern  sanitation,  that  the 
causes  of  many  infectious  diseases  are  preventable.  There  is  no  disease 
about  which  so  much  has  been  written  as  concerning  Asiatic  cholera,  the  mere 
list  of  titles  of  books  and  articles  on  this  subject  occupying  one  hundred 
and  forty-eight*  pages  in  the  great  Index  Catalogue  of  the  library  of  the 
surgeon-generaFs  office. 

Although  cholera  has  existed  in  parts  of  India  probably  from  time 
immemorial,  it  was  not  until  the  year  1817  that  it  spread  over  India,  and  in 
the  following  six  years  over  a  large  part  of  Asia.  The  second  cholera  pan- 
demic began  in  1826,  but  not  until  1831  did  it  reach  for  the  first  time  western 
Europe,  and  in  1832,  Canada  and  the  United  States.  Each  pandemic  of 
cholera  has  lasted  for  several  years,  during  which  the  disease  has  travelled 
over  most  of  tlie  inhabited  regions  of  the  globe,  only  a  few  remote  countries, 
such  as  the  islands  of  the  Pacific  ocean  and  Australia,  having  thus  far 
escaped.  According  to  the  usual  reckoning  the  present  is  the  sixth  of  the 
great  pandemics  of  cholera. 

The  sixty-two  years  which  have  passed  since  the  first  appearance  of  Asiatic 
cholera  in  western  Europe  have  witnessed  the  most  important  developments 
of  modern  hygiene.  It  is  interesting  to  note  to  what  extent  sanitary  science 
and  sanitary  works  have  been  influenced  by  the  occurrence  and  the  study 
of  this  disease. 


AND  SANITARY  REFORMS  601 

It  was  under  the  direct  impressions  of  the  first  terrible  visitation  of 
cholera  that  in  England  the  office  of  Registrar  General  was  established  and 
WiUiam  Farr  was  appointed  to  fill  it.  We  owe  to  this  office  and  to  the  work 
of  this  man  the  application  of  statistics  to  public  health.  As  has  been  said 
by  Dr.  Parkes,  an  English  hygienist,  "  It  is  impossible  for  any  nation,  or  for 
any  government,  to  remain  indifferent  when  in  figures  which  admit  of  no 
denial,  the  national  amount  of  health  and  happiness,  or  disease  and  suffer- 
ing, is  determined.  The  establishment  of  the  Registrar  General's  office  in 
1838,  and  the  commencement  of  the  system  of  accurately  recording  births 
and  deaths,  will  hereafter  be  found  to  be,  as  far  as  the  happiness  of  the 
people  is  concerned,  one  of  the  most  important  events  of  our  time.  We  owe 
a  nation's  gratitude  especially  to  him  to  whose  sagacity  the  chief  fruits  of 
the  inquiry  are  due,  William  Farr." 

The  English  have  taken  the  foremost  place  in  the  art  of  formulating  laws 
for  the  protection  of  health  and  in  the  organization  of  the  machinery  for 
public  health  administration,  which  is  entirely  of  modern  growth  as  a 
separate  department  of  government.  In  1832  the  dread  of  cholera  led  to  an 
act  of  Parliament,  empowering  the  privy  council  to  take  certain  preventive 
measures  against  the  spread  of  the  disease,  and  every  extensive  visitation  of 
cholera  has  been  followed  by  activity  in  the  passing  of  fresh  sanitary  acts. 
During  the  discussion  in  Parliament  in  1875  on  the  Public  Health  Act,  the 
most  complete  code  of  sanitary  law  in  existence,  Disraeli  said:  " The  public 
health  is  the  foundation  on  which  repose  the  happiness  of  the  people  and  the 
power  of  a  country.  The  care  of  the  public  health  is  the  first  duty  of  a 
statesman." 

A  decisive  part  in  the  development  of  the  doctrine  that  certain  infectious 
diseases  are  propagated  chiefly  through  impure  drinking  water  and  con- 
taminated soil  is  traceable  to  the  investigations  concerning  the  mode  of 
spread  of  cholera.  The  celebrated  instance  of  the  Broad  .street  pump  in 
London,  in  1854,  furnished  conclusive  evadence  that  the  cholera  poison  may 
be  conveyed  by  the  drinking  water.  A  distinguished  modem  hygienist  has 
said,  "  The  Broad  street  pump  has  played  not  only  a  decisive  role  in  the 
cholera  question,  but  it  has  furnished  also  the  most  important  impulse  for 
the  development  of  a  new  era  in  the  department  of  public  hygiene." 

That  pioneer  and  master  of  modern  hygiene.  Max  von  Pettenkofer,  bases 
to  a  large  extent  his  views  as  to  the  agency  of  contaminated  soil  in  the  spread 
of  certain  infectious  diseases,  upon  forty  years'  study  of  the  relations  of  the 
soil  to  the  distribution  of  cholera. 

These  views  widely  held  as  to  the  propagation  of  some  infectious  diseases 
by  the  drinking  water  and  by  the  soil,  and  based  so  largely  upon  the  study  of 
cholera,  have  been  not  of  theoretical  interest  only,  but  they  have  influenced 
41 


602  ASIATIC  CHOLERA 

profoundly  the  practical  measures  which  have  been  undertaken  to  preserve 
and  promote  the  health  of  the  people. 

Cholera  has  destroyed  millions  of  human  lives,  but  it  has  been  the  means 
of  saving  millions  more.  It  has  been  one  of  the  levers  of  progress  in  modern 
sanitation.  The  same  measures  which  are  needed  to  protect  a  city  against 
occasional  epidemics  of  cholera  are  needed  at  all  times  to  protect  it  against 
other  infectious  diseases,  such  as  typhoid  fever,  which  are  spread  in  a  similar 
manner,  and  which,  although  they  do  not  come  with  the  terrible  impetuosity 
of  cholera,  steadily  do  their  deadly  work,  and  in  the  course  of  time  destroy 
among  us  far  more  lives  than  cholera.  These  measures  for  the  sanitary 
welfare  of  the  people  should  be  provided  independently  of  the  danger  of 
cholera,  but  it  has  often  happened  that  governments  and  citizens  are  not 
aroused  by  the  common,  but  preventable,  causes  of  death  to  undertake  sani- 
tary works,  the  necessity  for  which  is  evident  enough  to  sanitarians.  Unfortu- 
nately, they  have  required  sometimes  the  violent  impressions  of  an  outburst 
of  cholera  to  stir  them  to  undertake  these  long-needed  sanitary  improve- 
ments. Witness  at  this  moment  Naples,  Marseilles,  and  Hamburg,  which  are 
spending  millions  of  dollars  for  destruction  of  insanitary  quarters,  for  bet- 
ter sewage  disposal,  for  improved  water  supply.  But  think  of  the  thousands 
of  lives  destroyed,  the  panic,  the  commercial  depression,  the  untold  misery 
through  which  these  cities  have  passed  before  the  warning  was  heeded. 

When  we  consider  the  properties  of  the  infectious  agent  of  cholera  and 
the  facts  established  concerning  the  mode  of  spread  of  the  disea.se,  it  is  not 
difficulty  to  understand  why  cholera  should  have  had  so  large  an  influence 
upon  th€  historical  development  of  modem  sanitary  science  and  art,  and  why 
measures  which  are  useful  in  preventing  the  invasion  and  propagation  of  this 
disease  are  applicable  also  to  typhoid  fever  and  some  other  infectious  dis- 
eases. There  have  been  and  still  are  conflicting  views  as  to  some  points  in 
the  causation  of  cholera,  but  as  to  many  points  there  is  substantial  unani- 
mity of  opinion. 

Asiatic  cholera  is  an  infectious  disease.  By  an  infectious  disease  is  meant 
one  which  is  produced  by  a  specific  microorganism  in  the  body.  Whether 
or  not  an  infectious  disease  is  contagious,  that  is,  communicable  from  person 
to  person,  depends  upon  the  properties  of  the  causative  microorganism,  and 
especially  upon  the  manner  in  which  this  organism  is  usually  eliminated 
from  the  body  and  must  be  received  in  order  to  cause  infection.  When,  as 
is  the  case  with  cholera,  the  infectious  germs  are  discharged,  .solely  or  chiefly, 
by  the  intestine,  and  must  be  taken  in  by  the  mouth  in  order  to  cause  the 
disease,  it  is  evident  that  the  disease  is  not  likely  to  be  conveyed  directly 
from  the  sick  to  the  healthy. 


AND  SANITARY  REFORMS  603 

The  species  of  bacterium  which  is  always  associated  with  Asiatic  cholera, 
and  which  there  is  the  best  reason  for  believing  to  be  the  cause  of  the  disease, 
is  usually  called  the  comma  bacillus  of  Koch,  from  its  shape  and  the  name 
of  its  discoverer. 

The  recognition  of  this  bacillus  is  the  only  absolutely  positive  means  of 
diagnosis  of  Asiatic  cholera.  After  the  establishment  of  an  epidemic  mis- 
takes in  diagnosis  are  not  likely  to  occur,  and  if  they  do,  they  are  of  little 
consequence,  but  it  is  important  that  a  bacteriological  examination  should 
be  made  in  the  earliest  suspected  cases,  in  order  that  suitable  preventive 
measures  may  be  taken. 

"One  of  the  most  important  properties  of  the  cholera  germ  is  that  it  is 
killed  in  a  short  time  by  complete  drying.  Bacteria  float  in  the  air  with 
particles  of  dust  only  when  they  have  been  desiccated.  Currents  of  air  are 
incapable,  under  ordinary  circumstances,  of  lifting  bacteria  from  moist  sur- 
faces. The  inference  is  therefore  justifiable  that  the  germs  of  cholera  are 
not  disseminated  through  the  atmosphere,  and  that  we  cannot  contract  the 
disease  by  taking  the  germs  in  with  the  air  which  we  breathe.  This  inference, 
which  is  a  most  comforting  one,  is  supported  by  observations  of  the  mode 
of  distribution  of  the  disease  and  is  manifestly  of  great  practical  importance 
as  regards  the  care  and  prevention  of  cases  of  cholera.  The  cholera  patient 
is  not  a  .source  of  danger  to  those  in  proximity  in  the  same  way  that  a 
smallpox  or  scarlet  fever  patient  is.  Neither  the  patient  nor  his  discharges 
infect  the  surrounding  air.  The  inhumanity  with  which  those  seized  with 
cholera  are  sometimes  treated  by  the  public  is  based  upon  groundless  ideas 
as  to  the  real  sources  of  danger. 

The  cholera  germs  must  be  taken  in  by  the  mouth  and  swallowed  in  order 
to  produce  the  disease  in  human  beings.  In  other  words,  the  principal 
sources  of  infection  are  the  drink  and  food,  sometimes  the  hands  or  other 
objects  contaminated  with  cholera  spirilla  and  brought  into  contact  with  the 
mouth. 

But  even  if  the  cholera  germs  in  this  way  gain  entrance  to  the  stomach, 
there  are  many  chances  that  they  will  not  produce  the  disease.  They  are 
weakened  or  killed  by  acids,  and  the  acidity  of  the  normal  juices  of  the 
stomach  is  an  obstacle  to  their  passage  in  a  living  and  virulent  condition 
into  the  intestine,  which  is  the  only  part  of  the  body  where  they  can  multiply 
and  flourish.  This  teaches  the  importance  of  a  healthy  stomach  in  cholera 
times,  and  the  danger  of  indiscretions  in  diet  or  in  other  ways,  which  impair 
the  functions  of  this  organ.  We  can  understand  why  during  epidemics  of 
cholera  there  is  often  a  marked  increase  in  the  number  of  cases  a  day  or  two 
after  the  carousing  of  a  popular  holiday  or  a  Continental  Sunday. 


604  ASIATIC  CHOLERA 

Aside  from  the  condition,  of  the  stomach'  there  appears  to  be  a  marked 
difference  in  individual  susceptibility  to  cholera.  A  large  number  of  persons 
do  not  contract  the  disease  even  when  exposed  to  its  causes.  Some  develop 
only  a  slight  or  moderate  diarrhoea,  which  would  not  ordinarily  attract 
attention,  although  cholera  spirilla  may  be  present  abundantly  in  the  in- 
testinal discharges.  Others  are  carried  off  in  a  few  hours  by  the  most  malig- 
nant type  of  the  disease.  To  what  extent  these  differences  depend  upon 
variations  in  susceptibility,  or  to  variations  in  the  virulence  of  the  cholera 
germs,  or  to  other  causes,  is  not  definitely  known,  but  we  know  enough  to 
indicate  tliat  among  our  prophylactic  measures  should  be  included  such  as 
tend  to  produce  and  to  preserve  individual  resistance  to  the  disease  so  fat  as 
this  is  within  our  control. 

It  is  well  known  that  the  largest  proportion  of  the  victims  of  epidemic 
cholera  is  among  the  crowded  poor  living  under  insanitary  conditions. 
Hence  it  is  plain  that  improvements  in  the  abodes  and  the  conditions  of 
living  of  this  class  will  do  much  to  lessen  the  chances  of  an  epidemic  of 
cholera.  Every  large  city  has  its  dangerous  spots,  which  may  become  breed- 
ing places  of  infectious  diseases,  and  the  thorough  overhauling  and  cleaning 
up,  often  indeed  the  destruction,  of  these  places  are  an  important  part  of 
municipal  sanitation. 

It  has  already  been  mentioned  that  the  cholera  germs  multiply  only  or 
chiefly  in  the  intestinal  tract  and  that  they  are  discharged  with  the  intestinal 
contents,  sometimes  with  the  vomit.  They  are  never  eliminated  with  the 
breath  or  from  the  surface  of  the  body.  The  real  danger  from  a  cholera 
patient  to  other  persons  is  in  his  discharges  and  in  objects  soiled  with  these 
discharges.  With  ordinary  care  and  in  decent  conditions  of  living  the 
chances  of  any  part  of  these  discharges  being  received  directly  into  the 
alimentary  tract  of  those  in  the  immediate  neighborhood  of  the  patient  are 
so  islight  that  cholera  is  not  ordinarily  regarded  as  contagious.  In  properly 
conducted  cholera  hospitals  instances  of  such  contagion  are  very  infrequent, 
but  in  the  crowded  homes  of  the  poor  such  instances  are  not  so  uncommon, 
so  that  in  every  large  epidemic  of  cholera  a  certain  number  of  cases,  par- 
ticularly in  the  so-called  house  epidemics,  are  attributable  to  contagion  iu 
the  sense  in  which  this  term  is  ordinarily  used. 

The  thorough  disinfection  of  the  discharges  of  cholera  patients  and  of 
objects  soiled  by  them  is  obviously  of  the  first  importance.  The  cheapest  and 
most  generally  applicable  and  efficient  of  the  disinfectants  for  the  discharges 
are  milk  of  lime  and  chloride  of  lime  of  good  quality.  One  of  the  great 
obstacles  to  checking  the  spread  of  the  disease  in  this  way  is  the  occurrence 
of  mild  cases,  which  are  not  recognized  as  cholera,  but  which  are  capable  of 
distributing  the  germs. 


AND  SANITARY  REFOEMS  605 

Outside  of  the  endemic  home  of  cholera,  in  southern  Bengal,  Asiatic  cholera 
is  always  to  be  referred  to  the  importation  of  the  cholera  germs,  although 
often  the  exact  time  and  mode  of  entrance  cannot  be  traced.  Human  beings 
and  their  effects  are  tlie  chief  carriers  of  these  germs.  Restraint  of  human 
intercourse  with  infected  localities  has  naturally  been  regarded  as  a  chief 
measure  of  protection.  The  achievements  of  quarantine  in  keeping  out 
cholera  have  been  relatively  to  its  vexations,  hardships,  cruelties,  and  inter- 
ference with  commerce  so  small  that  many  distinguished  sanitarians  would 
discard  it  altogether.  As  we  are  situated  in  this  country  it  would  doubtless 
be  unwise  to  relinquish  quarantine,  but  all  tlie  good  which  can  be  accom- 
plished by  quarantine  can  be  attained  by  scientific  and  humane  methods, 
which  should  be  uniform  and  under  unrestricted  national  control. 

The  public  should  realize  that  quarantine  is  at  best  an  uncertain  and  often 
inefficient  protection  against  cholera,  and  that  far  greater  safety  is  to  be 
sought  in  measures  which  render  the  city  or  locality  unsuitable  for  the 
multiplication  and  distribution  of  the  germs  of  the  disease.  All  great 
epidemics  of  cholera  are  referable  to  infection  of  the  locality.  One  of  the 
fundamental  facts  in  the  epidemiology  of  cholera  is  that  the  disease  has 
been  introduced  time  and  again  into  certain  places  without  spreading, 
whereas  at  other  times  or  in  other  places  the  introduction  of  a  single  case 
has  been  the  starting  point  of  a  terrible  epidemic.  There  are  cities  which  are 
naturally  immune  against  the  epidemic  spread  of  cholera;  there  are  other 
cities  which  have  made  themselves  virtually  cholera -proof.  It  is  this  pre- 
disposition in  time  and  in  place  wliich  has  been  and  is  still  the  subject  of 
much  of  the  controversial  literature  regarding  cholera. 

We  do  not  know  the  nature  of  all  of  the  local  and  seasonal  factors  con- 
cerned in  the  causation  of  epidemics  of  cholera,  but  concerning  some  we  have 
sufficient  information  to  indicate  the  line  of  action  to  be  pursued  in  en- 
deavoring to  make  a  place  unsuitable  for  the  spread  of  the  disease.  From 
what  has  already  been  said  in  this  article  it  is  clear  that  the  susceptibility 
of  a  place  to  cholera  must  depend  in  very  large  measure  upon  the  facility 
with  which  the  discharges  of  cholera  from  a  patient  can  get  into  the  soil  and 
into  the  sources  of  supply  of  the  drinking  water.  In  other  words,  the  charac- 
ters of  the  drainage,  of  the  disposal  of  sewage  and  of  the  water  supply  will 
often  decide  the  fate  of  a  city  when  cholera  has  been  introduced.  The  evidence 
that  some  of  the  great  epidemics  of  cholera  and  especially  of  the  explosive 
outbursts  of  the  disease  are  due  to  infection  of  the  water  supply  seems  con- 
clusive. The  recent  epidemic  in  Hamburg  will  be  cited  hereafter  as  a  classi- 
cal example  of  a  drinking  water  epidemic. 

The  lesson  to  be  learned  from  experience  seems  clear  enough.  A  city  can 
make  itself  nearly  if  not  wholly  immune  against  cholera.     This  requires 


GOG  ASIATIC  CHOLERA  AXD  SANITARY  REFORMS 

mucli  time,  money,  and  intelligence.  It  demands  the  aid  of  skilled  sanitary 
knowledge.  The  problems  of  municipal  sanitation  must  be  appreciated  by 
intelligent  public  opinion,  but  they  can  be  solved  only  by  those  who  have 
special  knowledge  and  who  are  trained  for  the  purpose.  The  necessity  of 
calling  in  the  assistance  of  skillful  sanitary  experts  for  the  work  of  municipal 
sanitation  is  one  of  the  most  important  objects  of  education  of  the  public  in 
sanitary  matters.  As  soon  as  there  is  a  demand  for  those  possessed  of  the 
requisite  training,  there  will  be  no  lack  of  the  supply. 

The  problems  of  protection  of  a  city  against  cholera  are  essentially  the 
problems  of  municipal  .sanitation  in  general.  They  relate  to  such  matters 
as  the  protection  of  the  water  supply  against  contamination ;  to  the  proper 
disposal  of  sewage;  to  good  drainage;  to  cleanliness  of  streets;  to  improve- 
ment or  removal  of  insanitary  quarters ;  to  thorough  sanitary  inspection ;  to 
the  provision  of  public  disinfecting  establishments,  public  bathing  places, 
and  hospitals  for  infectious  diseases ;  to  education  of  the  public  in  hygiene ; 
to  the  employment  of  sanitary  experts.  If  the  apprehension  of  an  invasion 
of  Asiatic  cholera  and  the  consequent  interest  in  sanitary  matters  should 
prove  the  incentive  to  sanitary  reforms,  there  will  result  permanent  increase 
in  happiness  and  health  and  the  prevention  of  other  infectious  diseases, 
which,  although  less  dreaded  because  they  are  more  familiar,  are  in  reality 
more  serious  and  constant  objects  of  concern  than  cholera. 


THE  RELATION  OF  SEWAGE  DISPOSAL  TO  PUBLIC  HEALTH' 

I  am  somewhat  perplexed  how  to  treat  the  subject  assigned  to  me,  for, 
although  it  is  a  very  broad  one,  its  various  parts  have  been  so  parcelled  out 
that  those  who  are  to  follow  will  take  up  most  of  the  points  which  would 
naturally  fall  within  my  theme. 

The  basis  of  modern  sanitation  is  the  recognition  of  the  fact  that  certain 
diseases,  particularly  those  called  infectious,  are  preventable.  So  familiar  is 
this  conception,  that  it  is  difficult  to  realize  that  it  is  essentially  of  modern 
origin.  While  it  is  true  that  in  all  ages  there  have  been  enlightened  physi- 
cians to  whom  this  conception  of  the  preventability  of  disease  was  not  entirely 
foreign,  nevertheless  the  prevailing  opinion  in  ancient  and  medieval  times 
referred  the  origin  of  epidemic  diseases  to  such  supposed  causes  as  the  anger 
of  an  offended  Deity,  the  influence  of  the  planets  and  comets,  poisoning  of 
wells  by  the  Jews,  some  mysterious  epidemic  constitution  of  the  atmosphere, 
etc.  Under  the  control  of  such  ideas,  it  is  clear  that  public  and  private  sani- 
tation could  not  develop.  Certain  great  public  works  of  antiquity  to  which 
we  must  attach  hygienic  value,  such  as  the  momumental  aqueducts  and 
drains  of  ancient  Eome,  were  undertaken  for  public  convenience  and  not 
with  any  clear  appreciation  of  their  relations  to  public  health. 

The  doctrine  of  the  preventability  of  infectious  diseases  was  first  estab- 
lished upon  a  firm  basis  by  the  collection  and  analysis  of  vital  statistics. 
This  great  contribution  to  preventive  medicine  we  owe  to  the  establishment 
of  the  Registrar  General's  Office  in  England,  in  1838,  concerning  which  an 
English  hygienist  has  justly  said :  "  It  is  impossible  for  any  nation  or 
for  any  government  to  remain  indifferent  when  in  figures  which  admit  of  no 
denial  the  national  amount  of  health  and  happiness,  or  disease  and  suffering, 
is  determined.  The  establishment  of  the  Registrar  General's  Office  in  1838, 
and  the  commencement  of  the  system  of  accurately  recording  births  and 
deaths,  will  hereafter  be  found  to  be,  as  far  as  the  happiness  of  the  people 
is  concerned,  one  of  the  most  important  events  of  our  time." 

The  impetus  which  led  to  this  systematic  collection  and  study  of  vital 
statistics,  as  well  as  to  other  great  sanitary  reforms,  was  the  invasion  of 

^Remarks  made  before  the  Joint  Meeting  of  the  Medical  and  Chirurgical 
Faculty  of  Maryland  and  the  Maryland  Public  Health  Association,  to  discuss 
the  Sewage  Disposal  of  Baltimore,  Baltimore,  November  19,  1897. 

Maryland  M.   J.,  Bait,  1897-98,  XXXVIII,  199-204. 

607 


608  SEWAGE  DISPOSAL  AND  PUBLIC  HEALTH 

Asiatic  cholera  for  the  first  time  into  Western  Europe  in  1831.  The  careful 
study  of  the  mode  of  spread  of  this  pestilence  led  to  the  clear  recognition  of  the 
fact  tliat  it  is  a  preventable  disease,  and  it  was  soon  discovered  that  the  same 
conception  is  applicable  to  typhus  fever,  typhoid  fever  and  many  other  infec- 
tious diseases.  Cholera  has  destroyed  millions  of  human  lives,  but  it  has 
been  the  indirect  means  of  saving  millions  more. 

The  visitation  of  great  epidemic  diseases,  such  as  cholera  and  yellow  fever, 
has  been  one  of  the  levers  of  progress  in  modern  sanitation.  Although  we 
have  constantly  with  us  diseases,  notably  typhoid  fever,  which  teach  the 
same  lessons  and  are  as  preventable  as  cholera,  it  has  often  required  the 
violent  impressions  of  the  outburst  of  some  rapidly  spreading  and  strange 
pestilence  to  stir  a  community  to  undertake  sanitary  improvements,  whose 
necessity  has  been  long  pointed  out  by  sanitarians.  We  in  Baltimore  can, 
if  we  choose,  wait  to  receive  such  a  violent  lesson,  but  it  is  the  part  of  wisdom 
and  prudence  to  profit  by  the  same  lesson  which  existing  circumstances 
teach  no  less  distinctly,  even  if  with  less  impetuosity. 

It  is  fortunate  that  those  who  instituted  the  first  public  sanitary  measures 
did  not  wait  to  find  a  thoroughly  scientific  basis  for  them.  Even  in  this  day 
with  our  greatly  extended  knowledge  of  the  causation  and  mode  of  spread 
of  infectious  diseases,  there  are  many  proved  measures  for  preventing  the 
development  and  spread  of  disease,  for  which  we  cannot  give  an  entirely 
satisfactory  scientific  explanation.  We  must  utilize  the  results  both  of 
practical  experience  and  of  scientific  investigation  in  determining  the  charac- 
ter and  the  eflficacy  of  sanitary  procedures. 

The  early  English  sanitarians  based  their  practical  sanitary  measures 
upon  a  belief  in  the  efficacy  of  cleanliness  in  preventing  the  development 
and  extension  of  infectious  diseases,  and  they  directed  their  efl'orts  espe- 
cially to  securing  pure  soil  to  live  upon,  pure  air  to  breathe,  pure  water  to 
drink,  and  pure  food  to  eat.  While  modern  bacteriology  has  taught  us  the 
particular  impurities  in  our  environment  most  to  be  dreaded  and  conse- 
quently better  means  to  guard  against  them,  this  programme  of  the  early 
sanitarians  remains  to  this  day  the  broadest  and  most  satisfactory  basis  of 
preventive  medicine. 

While  the  great  media  of  our  environment,  soil,  water,  air,  and  food,  are 
so  intimately  associated  in  their  sanitary  relations,  that  impurities  of  one 
are  likely  to  affect  others,  my  theme  on  this  occasion  relates  especially  to  the 
dangers  of  pollution  of  the  soil. 

The  soil  is  the  place  to  which  sooner  or  later  all  organic  matter  returns. 
From  it  comes  all  life  and  to  it  all  life  returns.  "  Dust  thou  art,  and  unto 
dust  shalt  thou  return,"  embodies  a  profound  scientific  truth.  The  soil  is 
the  greatest  laboratory  in  the  world.     It  is  there  through  the  agency  of 


SEWAGE  DISPOSAL  AND  PUBLIC  HEALTH  609 

microscopic  organisms  that  organic  matter  derived  from  plants  and  animals 
is  decomposed  and  converted  finally  into  the  simple  inorganic  substances 
which  make  the  food  of  plants.  The  plants  again  build  up  these  simple 
mineral  constituents  into  the  complex  organic  materials  of  their  bodies,  which 
make  the  food  of  animals.  In  this  continual  circulation  of  matter,  agencies 
at  work  in  the  soil  play  an  indispensable  part,  a  part  so  essential  that  if  this 
link  in  the  chain  should  drop  out  all  life  upon  this  globe  would  cease  in  a 
comparatively  short  time. 

It  is  through  these  agencies,  which  are  chiefly  living  microorganisms 
present  everywhere  in  the  superficial  soil,  that  the  soil  is  able  to  dispose  of 
organic  matter  which  it  receives  and  thus  continually  to  purify  itself.  Upon 
tliis  principle  is  based  the  method  of  disposal  of  sewage  by  irrigation  and 
filtration  through  the  soil.  But  there  is  a  limit  to  the  capacity  of  soil  to  con- 
vert organic  material  into  a  harmless  state  and  if  this  limit  is  exceeded  we 
have  a  polluted  soil.  There  are  likewise  various  circumstances,  which  cannot 
be  considered  here,  which  influence  the  rapidity  and  extent  of  this  process  of 
self-purification.  For  example,  when  the  organic  material  is  not  received 
upon  the  superficial  layers  of  the  soil,  but  leaks  out,  as  through  cesspools,  into 
the  deeper  layers,  the  process  of  purification  is  much  slower  and  less  eSica- 
cious.  In  this  way  the  soil  may  become  contaminated  to  great  depths  and 
may  bring  serious  injury  to  people  living  upon  it.  There  are  various  artifi- 
cial conditions,  such  as  pavements,  which  render  much  of  the  ground  in  cities 
incapable  of  doing  the  work  of  virgin  soil  in  transforming  organic  waste. 

What  are  the  dangers  of  such  contamination  of  the  soil?  Some  of 
these  dangers  we  can  point  out  with  reasonable  certainty ;  others,  which  we 
have  reason  to  believe  exist  in  view  of  certain  benefits  which  regularly  follow 
purification  of  the  soil,  we  understand  at  present  either  very  imperfectly  or 
not  at  all. 

Pettenkofer  has  called  especial  attention  to  the  fact  that  the  air  in  the  lower 
parts  of  our  houses  is  derived  in  no  small  part  from  air  drawn  from  the 
ground,  unless  the  special  construction  of  the  cellars  prevents  this.  If  this 
ground  air  comes  from  a  polluted  soil,  it  contains  foul  gases,  the  precise 
influence  of  which  upon  the  health  of  the  inhabitants  it  has  not  yet  been 
found  possible  to  determine,  but  there  is  reason  to  believe  that  it  may  be 
injurious,  and  certainly  it  must  be  regarded  as  offensive.  That  such  air 
under  certain  circumstances  may  contain  disease-producing  microorganisms 
is  highly  probable.  When  the  soil  has  become  saturated  with  illuminating 
gas  derived  from  leaky  or  broken  gas  pipes,  the  air  of  houses  in  the  neighbor- 
hood may  become  so  contaminated  with  gas  drawn  in  from  the  soil,  that 
serious  poisoning  of  the  inhabitants  may  result,  as  has  repeatedly  been 
observed. 


610  SEWAGE  DISPOSAL  AND  PUELIC  HEALTH 

The  view  is  widely  held  that  serious  contamination  of  the  soil  is  injurious 
to  the  health  of  those  living  upon  it,  independently  of  the  actual  presence  in 
euch  soil  of  the  specific  germs  of  disease.  Exposure  to  such  influences  is 
thought  to  be  capable  of  impairing  mental  and  physical  vigor  and  in  general 
of  lowering  resistance  to  disease.  Among  the  various  factors  which  deter- 
mine the  higher  death  rate  in  many  crowded  and  insanitary  localities,  pol- 
lution of  the  ground  is  doubtless  one  of  importance. 

It  is,  however,  more  especially  in  the  presence  of  the  specific  microorgan- 
isms which  cause  infectious  diseases,  that  we  have  to  seek  the  chief  dangers 
from  contamination  of  the  soil  with  human  and  animal  excreta  and  house- 
hold waste.  Without  proper  methods  of  disposal  of  sewage  abundant  oppor- 
tunities are  afforded  for  the  escape  of  such  pathogenic  microorganisms  into 
the  soil. 

The  fate  of  such  organisms  after  they  have  reached  the  soil  is  various.  It 
has  been  demonstrated  that  the  bacilli  of  tuberculosis  and  of  typhoid  fever 
may  survive  months,  perhaps  even  years,  and  that  those  of  cholera  may  per- 
sist for  weeks  in  the  soil.  Whereas  in  virgin  soil  they  do  not  find  requisite 
food  for  their  multiplication,  the  bacilli  of  typhoid  fever  may  actually  mul- 
tiply in  soil  contaminated  with  organic  material. 

Having  once  reached  the  soil,  these  disease-producing  germs  may  be  con- 
veyed to  us  in  manifold  ways.  An  important  medium  of  transportation  of 
bacteria  from  an  infected  soil  is  the  water  which  we  drink  or  use  for  domestic 
purposes.  Our  chief  interest  here  in  Baltimore  in  the  contamination  of  drink- 
ing water  from  the  soil  relates  not  to  our  own  soil,  save  in  the  occasional 
use  of  wells,  especially  in  the  recently  annexed  districts,  but  relates  to  that 
bordering  on  the  streams  and  reservoirs  from  which  we  receive  our  naturally 
excellent  drinking  water.  It  is,  therefore,  not  necessary  to  dwell  upon  this 
point  on  this  occasion. 

Among  the  various  other  ways  by  which  harmful  bacteria  may  reach  us 
from  contaminated  ground  it  will  suffice  to  specify  their  conveyance  attached 
to  particles  of  dust  in  the  air,  their  transportation  by  flies  and  other  insects, 
and  by  domestic  animals,  their  presence  upon  vegetables,  especially  those 
eaten  uncooked,  and  our  own  direct  contact  with  the  soil.  It  is  evident  that 
the  possibilities  of  infection  from  soil  contaminated  with  disease  germs  are 
numerous  and  often  intricate. 

The  list  of  diseases  whose  causation  has  been  shown  to  stand  under  certain 
conditions  in  more  or  less  direct  relation  to  contamination  of  the  ground 
with  their  specific  germs  is  a  long  one.  Among  the  more  important  may  be 
mentioned  malaria,  typhoid  fever,  cholera,  yellow  fever,  dysentery,  tubercu- 
losis and  the  summer  diarrhoeas  of  infants.  Experience  teaches,  unmistak- 
ably, that  contamination  of  the  soil  with  organic  refuse  favors  the  develop- 


SEWAGE  DISPOSAL  AND  PUBLIC  HEALTH  611 

ment  and  spread  of  such  diseases  as  these,  and  that  drainage  and  purification 
of  the  soil  by  proper  systems  of  sewerage  are  among  the  most  effective 
measures  for  their  prevention. 

No  more  instructive  illustration  of  the  value  of  modern  methods  of  public 
sanitation  can  be  found  than  the  inability  of  Asiatic  cholera  to  secure  a 
foothold  during  the  last  two  European  epidemics  in  clean  cities  with  proper 
sewerage  and  water  supply  and  its  ravages  in  notoriously  filthy  or  insanitary 
cities,  such  as  Toulon,  Marseilles,  Naples  and  formerly  Hamburg.  The 
public  should  realize  that  quarantine  is  an  extremely  vexatious,  expensive, 
uncertain,  means  of  protection,  and  that  far  .greater  safety  can  be  secured  by 
measures  which  render  a  city  unsuitable  for  the  multiplication  and  distri- 
bution of  the  germs  of  epidemic  diseases.  A  city  can  make  itself  cholera- 
proof  by  well  understood  sanitary  measures. 

Insanitary  conditions,  to  adopt  a  metaphor  employed  by  Pettenkofer, 
represent  the  powder  and  the  germs  of  cholera  or  typhoid  fever  sparks.  It 
is  wiser  to  keep  no  powder  of  this  sort  than  to  engage  in  frenzied  and  often 
futile  efforts  to  drive  away  the  sparks  which,  if  they  reach  the  powder,  will 
cause  a  destructive  explosion. 

Although  the  nature  of  the  relationship  between  the  conditions  of  the 
ground  and  the  prevalence  of  tuberculosis  is  not  well  understood,  practical 
experience  has  shown  that  many  localities  have  secured,  by  good  drainage  of 
the  soil,  great  reduction  in  the  mortality  from  this  most  deadly  scourge  of 
the  human  race,  a  reduction  amounting  in  some  places  to  nearly  fifty  per  cent, 
of  the  former  death  rate.  Similar  measures  in  Berlin  and  elsewhere  have 
notably  lowered  the  mortality  among  infants,  particularly  from  summer 
diarrhoea. 

I  call  your  attention  to  these  various  charts  hung  upon  the  wall  which 
illustrate  some  of  the  beneficial  results  which  have  been  secured  by  purifica- 
tion of  the  soil  through  proper  systems  of  sewerage.  The  charts  speak  for 
themselves. 

Upon  this  one  the  black  column  represents  the  average  number  of  deaths 
from  typhoid  fever  in  313  cities  without  sewers  and  the  next  column,  less 
than  one-quarter  of  the  first  in  height,  shows  the  deaths  in  39  cities  with 
efficient  sewers. 

This  second  chart  shows  on  the  left  side  the  deaths  from  typhoid  fever  to 
each  10,000  inhabitants  in  each  of  a  series  of  cities  with  good  sewers  and  a 
general  water  supply,  and  upon  the  right  side  the  deaths  from  the  same 
cause  in  cities  without  sewers  or  very  imperfectly  sewered.  You  will  observe 
that  the  average  in  the  first  series  is  2.4  and  in  the  second  is  10,  with  many 
cities  lower  than  the  average  in  the  first  series,  notably  Munich,  Dantzic, 


612  SEWAGE  DISPOSAL  AND  PUBLIC  HEALTH 

Vienna  and  Frankfort,  and  many  higher  than  the  average  in  the  second  series, 
notably  several  Italian  cities. 

Especially  instructive  is  the  next  chart,  vrhich  shows  the  experience  of 
Munich  during  the  gradual  improvement  of  an  originally  highly  contami- 
nated soil.  During  the  first  period  represented,  when  the  inhabitants  drank 
water  from  wells  and  the  excreta  were  stored  in  ordinary  privy  vaults,  the 
death  rate  from  typhoid  fever  was  24.2  per  10,000  inhabitants.  When  the 
city  required  the  cementing  of  the  vaults,  the  death  rate  fell  to  16.6,  The 
remaining  three  lines  show  the  successive  reductions  in  the  death  rates  with 
the  gradual  extension  of  the  sewerage  system,  until  in  1884  the  deaths  from 
.this  fever  were  reduced  to  1.4  per  10,000,  and  in  1888  to  1  per  10,000  inhab- 
itants. By  systematic  and  intelligently  directed  sanitary  improvements  the 
cities  of  ^Nlunich  and  Vienna  have  been  converted  from  hot-beds  of  typhoid 
fever  to  places  from  which  this  disease  has  been  practically  eradicated.  All 
of  the  money  which  they  have  expended  in  carrying  out  these  great  sanitary 
reforms  has  been  repaid  a  hundredfold  in  the  increased  health,  happiness 
and  productive  capacity  of  the  inhabitants  and  in  the  increased  value  of 
property. 

The  same  results  can  be  secured  by  Baltimore  and  other  cities,  as  is  demon- 
strated by  this  chart,  which  shows  for  Dantzic,  Breslau,  Frankfort,  Berlin, 
Vienna,  Brussels,  London,  New  York,  Boston,  Brooklyn,  and  other  cities  the 
deaths  from  typhoid  fever  to  each  10,000  inhabitants  before,  during  and 
since  the  introduction  of  sewerage  and  general  water  supply.  You  will  ob- 
serve that  the  experience  has  been  everywhere  the  same,  lowering  of  the  death 
rate  to  a  quarter,  a  sixth,  an  eighth,  a  twelfth,  even  a  twentieth,  of  the  former 
rate. 

This  red  line  represents  the  mortality  from  typhoid  fever  in  Baltimore. 
It  is  the  official  mortality  from  this  disease.  The  actual  mortality  is  con- 
siderably higher,  for,  as  Dr.  Osier  has  pointed  out,  doubtless  most  of  tlie 
deaths  in  this  city  returned  to  the  Health  Department  as  from  malarial  fever 
and  from  typho-malarial  fever  are  in  reality  due  to  typhoid  fever.  The  death 
rate  from  typhoid  fever  in  this  city,  as  he  has  shown,  is  that  which  belongs 
to  an  unsewered  city  with  general  water  supply,  and  it  can  be  confidently 
predicted  that  the  introduction  of  efficient  sewerage  and  the  protection  of  the 
sources  of  our  water  supply  will  reduce  this  mortality  to  the  low  rate  of  well 
sewered  and  well  watered  cities. 

The  reduction  in  typhoid  fever  shown  by  the  charts  cannot  be  attributed 
wholly  to  the  introduction  of  good  sewers.  In  many  instances  it  has  been 
due  mainly  to  the  introduction  of  a  general  supply  of  pure  drinking  water. 
Authorities  have  differed  as  to  the  relative  value  of  sewerage  and  of  water 
supply  in  influencing  the  prevalence  of  typhoid  fever.    We  need  not  pause 


SEWAGE  DISPOSAL  AND  PUBLIC  HEALTH  613 

here  to  discuss  this  matter.  Both  factors  are  important,  the  drinking  water 
usually  the  more  important.  But  it  is  sufficient  for  our  purpose  to  show 
that  purification  of  the  ground  by  proper  disposal  of  sewage  is  one  of  the 
factors  in  determining  a  reduction  in  the  occurrence  of  typhoid  fever  and 
other  diseases. 

It  is  by  no  means  an  easy  matter  in  all  cases  to  assign  to  each  one  of  the 
various  recognized  elements  which  go  to  make  up  an  entire  system  of  satis- 
factory municipal  sanitation  its  due  share  in  the  beneficial  result,  for  it 
rarely  happens  that  one  is  introduced  by  itself  alone,  and  the  harmonious 
working  of  the  whole  system,  is  often  necessary  to  secure  the  best  results  from 
the  individual  factors,  such  as  pure  water-supply,  efficient  sewerage,  good 
drainage,  cleanliness  of  streets,  improvement  or  removal  of  insanitary  quar- 
ters, thorough  sanitary  inspection  of  dairies  and  food-stuffs,  public  disinfec- 
ting establishments,  hospitals  for  infectious  diseases,  municipal  laboratories, 
etc.  In  some  instances,  however,  the  conditions  have  been  such  as  to  furnish 
conclusive  demonstration  of  the  separate  influence  of  the  introduction  of 
effective  sewerage  upon  the  death  rate  from  typhoid  fever.  This  is  notably 
true  of  Dantzic  and  Stockholm,  as  is  illustrated  by  these  charts.  In  the 
former  city  a  high  death  rate  from  typhoid  fever  persisted  after  a  good 
general  water  supply,  but  after  the  introduction  of  the  system  of  sewerage 
it  fell  from  nearly  10  per  10,000  to  1.5.  You  will  observe  in  this  striking 
chart  how  in  the  city  of  Stockholm  the  mortality  from  typhoid  fever  fell, 
pari  passu,  with  the  gradual  extension  of  the  sewerage  system,  reaching  in 
1887  the  low  figure  of  1.7  per  10,000. 

Much  more  e\adence  might  be  adduced,  if  it  were  necessary,  to  show  the 
beneficial  influence  of  good  sewerage  upon  the  health  of  a  community,  but 
enough  has  already  been  said  to  demonstrate  the  hygienic  importance  of 
proper  disposal  of  sewage.  Indeed  it  might  seem  unnecessary  to  dwell  upon 
these  matters  upon  which  sanitarians  are  agreed,  were  it  not  that  public 
indifference  to  this  subject  indicates  lamentable  ignorance,  although  for  two 
generations  the  gospel  of  public  sanitation  has  been  preached  to  this  city  by 
its  health  officers  and  others.  Trite  and  wearisome  as  the  tale  may  be, 
it  is  one  which  must  be  told  and  retold  and  we  cannot  choose  but  hear  until 
the  end  desired  is  attained. 

But  it  is  not  necessary  or  even  desirable  to  rest  the  argument  for  an  efficient 
sewerage  system  exclusively  upon  its  effects  on  public  health,  important  as 
these  are.  Quite  apart  from  the  large  saving  of  human  life,  the  proper  dis- 
posal of  excreta,  household  waste,  water  and  garbage  contributes  so  much 
to  the  comforts,  conveniences  and  even  decencies  of  living  and  so  essential  a 
part  of  such  disposal  in  large  cities  is  a  good  system  of  drains  and  sewers, 
that  it  is  positively  uncivilized  for  a  modern  city  to  be  deprived  of  the 


614  SEWAGE  DISPOSAL  AND  PUBLIC  HEALTH 

advantages  of  such  a  system.  The  conditions  in  this  respect  here  in  Balti- 
more with  its  leaky  and  overflowing  surface  drains,  with,  its  utterly  insuffi- 
cient storm  water  drains,  with  one-twentieth  of  its  area,  exclusive  of  streets 
and  parks,  occupied  by  privy  pits  and  cesspools,  permitting  often  overflow 
and  leakage  into  the  ground  and  cellars,  with  arrangements  by  which  sew- 
age and  garbage  are  allowed  to  befoul  the  streams  and  the  harbor  basin,  are 
obnoxious  in  the  extreme.  That  greater  damage  to  health  and  property  has 
not  been  the  result  of  these  primitive  conditions  is  due  in  large  part  to  the 
natural  salubrity  of  the  city  and  the  configuration  and  character  of  the 
ground. 

Mr.  Mendes  Cohen,  in  a  publislied  address  delivered  before  the  Taxpayers' 
Association  of  Baltimore  about  six  years  ago,  pointed  out  very  clearly  and 
forcibly  the  injury  to  property  caused  by  the  defective  drainage  of  this  city 
and  he  showed  how  the  rental  value  of  property  would  be  so  much  enhanced 
by  the  introduction  of  good  drainage  that  a  large  share  of  the  necessary  cost 
of  the  improvements  would  be  thereby  covered.  Dr.  Fulton  will  tell  you  this 
evening  something  about  the  loss  in  money  due  to  sickness  and  death  entailed 
by  the  present  conditions  and  the  estimated  pecuniary  gain  which  can  reason- 
ably be  expected  to  follow  the  establishment  of  a  good  system  of  sewers.  But 
who  can  estimate  the  suspense,  the  suffering,  the  grief,  the  despair  caused  by 
the  unnecessary  sickness  and  sacrifice  of  life  through  neglect  of  the  plainest 
laws  of  sanitation  ? 

The  immediate  occasion  of  our  assembling  this  evening  upon  the  call  of 
the  physicians  and  sanitarians  of  this  state  is  the  consideration  of  the 
recently  published  Eeport  of  the  Sewerage  Commission  of  the  City  of  Balti- 
more, of  which  an  abstract  has  been  presented  to  you  by  Dr.  McShane. 
Those  who  are  to  follow  me  will  discuss  the  details  of  this  Report.  It  seems 
to  me  to  be  an  admirable  document,  supplying  as  it  does  the  necessary  data, 
based  upon  a  careful  and  scientific  investigation  of  the  problems  involved, 
to  enable  the  reader  to  form  an  intelligent  judgment  upon  the  subject.  It 
would  be  a  great  misfortune  if  the  city  of  Baltimore  should  not  take  advan- 
tage of  this  opportunity  to  come  to  some  definite  solution  of  this  problem 
which  must  be  solved  sooner  or  later  and  which  becomes  more  complicated 
the  longer  it  is  deferred.  It  behooves  our  citizens  and  above  all  our  legis- 
lators to  give  earnest  heed  to  this  matter  and  to  see  to  it  that  this  Eeport  does 
not  remain  as  fruitless  in  practical  results  as  did  its  predecessors. 


EELATIONS  OF  LABORATOEIES  TO  PUBLIC  HEALTH ' 

Mr.  President  and  Members  of  the  American  Public  Health  Association: 
I  am  very  glad  of  the  opportunity  of  appearing  before  you,  and  desire  to 
say  a  few  words  with  reference  to  the  general  subject  of  the  relations  of 
laboratories  to  public  health.  A  laboratory  is  a  workshop  where  those,  who 
are  suitably  trained,  have  charge  of  the  work  which  is  done,  where  they  have 
the  proper  supply  of  material  and  adequate  means  for  carrying  out  the  study 
of  such  material.  Such  laboratories  may  be  used  for  different  purposes. 
Some  of  them  we  may  regard  as  private  laboratories ;  some  as  purely  investi- 
gating laboratories;  others  are  intended  for  purposes  of  instruction,  and 
still  others  are  mainly  to  make  available  to  the  general  public  the  results  of 
scientific  work  by  tlie  conduct  of  certain  technical  procedures.  Laboratories 
in  one  form  or  another  have  existed  from  the  earliest  times.  We  must 
suppose  that  Aristotle  had  something  in  the  nature  of  a  laboratory,  and 
although  we  know  very  little  definitely  about  the  remarkable  Alexandrian 
period  in  medicine  and  science,  it  is  clear  that  laboratories  must  have  existed 
then.  But  public  laboratories,  which  were  freely  opened  for  purposes  of 
instruction  and  investigation,  are  modern.  With  the  exception  of  the  ana- 
tomical laboratory,  which  has  existed  in  some  form  since  the  fifteenth  cen- 
tury, laboratories,  as  now  understood,  are  the  creation  of  the  present  century. 

It  is  usually  stated  that  the  first  laboratory  in  a  modern  sense  was  the 
chemical  laboratory  founded  by  von  Liebig  in  1825.  This  is  not  strictly 
correct  as  a  physiological  laboratory  was  established  by  Purkinje  in  Breslau 
in  1824.  It  nevertheless  remains  true  that  Liebig's  laboratory  had  the 
greatest  influence  upon  the  subsequent  development  of  laboratories  through- 
out the  world,  and  to  this  day  our  chemical  laboratories  are  the  best  sup- 
ported and  best  equipped  laboratories  which  we  possess.  I  shall  not 
attempt  to  trace  the  evolution  of  laboratories  up  to  the  present  time.  But 
it  is  of  interest  to  note  the  very  recent  development  of  laboratories  devoted 
to  the  study  of  hygiene. 

The  first  laboratory  of  hygiene  was  started  by  von  Pettenkofer  in  Munich 
and  opened  for  students  and  investigators  in  1878.  It  is  rather  surprising 
that  the  existence  of  public  hygienic  laboratories  goes  back  only  to  that 

^  Report  of  an  address  delivered  before  American  Public  Health  Association, 
Minneapolis,  Minn.,  October  31,  1899. 

Am.  Pub.  Health  Ass.  Rep.,  1899,  Columbus,  1900,  XXV,  460-465. 

615 


616  LABORATORIES  AND  PUBLIC  HEALTH 

quite  recent  period,  and  those  of  you,  who  are  familiar  with  the  outcome  of 
the  foundation  of  that  remarkable  laboratory  in  Munich,  know  that  it  was 
one  which  included  all  departments  of  hygiene  in  the  broadest  sense — the 
physical  side,  the  chemical  side,  the  bacteriological  side  of  hygiene,  all  rep- 
resented there  by  separate  departments  with  the  respective  directors  of  these 
departments.  What  inestimable  benefits  it  has  brought  to  the  city  of 
Munich!  In  this  laboratory  were  investigated  the  great  problems  relating 
to  the  disposal  of  sewage,  the  public  water  supply,  the  factors  concerned  in 
the  prevalence  of  epidemic  diseases,  and  more  especially  of  cholera  and 
typhoid  fever.  The  well-known  doctrine  as  to  the  relation  of  typhoid  fever 
to  ground-water  was  promulgated  and  thoroughly  discussed.  The  result  has 
been  of  inestimable  value  to  the  inhabitants  of  that  city — a  city  which  was 
once  the  very  hotbed  of  typhoid  fever,  and  which,  at  the  present  day,  is  prac- 
tically free  from  it,  so  that  I  have  heard  von  Ziemssen  say  that  he  has  found 
it  extremely  difficult  to  give  practical  demonstrations  to  medical  students 
of  the  lesions  of  this  disease.  The  great  work  of  von  Pettenkofer  and 
his  coadjutors  cannot  be  expressed  in  dollars  and  cents. 

A  great  impulse  to  the  foundation  of  hygienic  laboratories  came  about  this 
period  from  the  epochal  discoveries  in  bacteriology.  It  was  then  that  Koch 
introduced  his  remarkably  simple  methods  for  the  isolation  and  study  of 
bacteria  of  certain  infectious  diseases.  The  stimulus  from  these  great  dis- 
coveries led  to  the  very  rapid  foundation  of  hygienic  laboratories  in  connec- 
tion with  universities,  so  that  within  a  few  years  nearly  all  of  the  great  univer- 
sities in  Germany  were  provided  with  such  laboratories.  Another  factor  which 
has  exerted  a  great  influence  in  the  development  of  hygiene  has  been  the 
occurrence  of  epidemic  diseases,  more  particularly  such  diseases  as  cholera, 
and  in  this  country  also  yellow  fever,  and  possibly  it  may  turn  out  in  the 
East  that  the  plague  may  have  a  similar  influence  upon  public  sanitation 
there.  Devastating  as  these  diseases  have  been,  it  is  a  question  whether  the 
final  outcome  has  not  been  on  the  whole  to  the  advantage  of  the  human  race, 
because  it  does  often  seem  as  if  it  required  the  violent  impressions  of  such 
pestilences  to  stir  the  people  up  to  an  appreciation  of  the  needs  of  sanitation 
which  are  realized  by  sanitarians  themselves,  but  who  find  it  very  hard  to 
bring  these  matters  to  the  attention  of  the  public  in  a  forcible  way.  ]  As  the 
result  then  of  the  very  natural  development  of  laboratories  in  general,  of  the 
developments  in  bacteriology  and  of  the  lessons  of  epidemic  diseases,  we  have 
witnessed  during  the  last  twenty  years  the  rapid  foundation  of  hygienic  lab- 
oratories connected  particularly  with  universities,  and  with  boards  of  health, 
both  municipal  and  state.  It  is  more  particularly  with  reference  to  the  latter 
laboratories,  connected  with  municipal  and  state  boards  of  health,  that  we 
are  especially  interested. 


LABORATORIES  AND  PUBLIC  HEALTH  617 

It  will  be  appropriate  to  say  a  few  words  with  reference  to  the  development 
and  organization  of  such  laboratories,  the  important  results  which  have  been 
achieved  and  the  prospects  which  we  can  reasonably  expect  from  their  work. 
These  laboratories,  as  you  already  know,  have  been  founded  in  large  number 
in  this  country,  and,  in  fact,  the  development  of  laboratories  connected  with 
boards  of  health  is  one  which  is  peculiarly  American.  The  appreciation  of 
the  need  of  such  laboratories,  of  what  can  be  accomplished  by  them  and  of 
the  benefits  which  the  general  public  derive  from  them,  has  been  greater 
in  this  country  than  elsewhere.  We  have  led  in  this  particular  direction. 
The  work  of  these  municipal  and  state  laboratories  should  in  the  first  place, 
be  put  in  charge  of  those  who  are  especially  trained  in  modern  methods  in 
bacteriology,  in  chemistry,  in  hygiene  and  in  pathology.  These  are  very  often 
the  younger  men  who  have  had  opportunities  for  these  special  lines  of  study. 
Such  laboratories  are,  in  a  few  instances,  well  supported,  better  supported 
than  the  laboratories  in  connection  with  universities.  The  kinds  of  work 
undertaken  in  these  laboratories  relate  more  particularly  to  practical  prob- 
lems concerned  in  the  diagnosis,  prevention  and  cure  of  disease ;  whereas  the 
broader  biological  aspects  are  more  properly  considered  in  laboratories  which 
belong  to  colleges  and  universities.  But  it  has  been  difficult  indeed  for  med- 
ical colleges  and  universities  to  supply  suitable  laboratories.  They  are 
expensive,  and  comparatively  few  of  the  educational  institutions  of  this 
country  are  supplied  with  anything  which  is  worthy  of  the  name  of  a  hygienic 
laboratory.  I  think  one  could  count  upon  the  fingers  of  one  hand  the  lab- 
oratories connected  with  medical  colleges  or  universities  in  this  country 
which  are  appropriately  called  hygienic  laboratories,  not  that  hygiene  is  not 
represented  in  a  larger  proportion  than  that,  but  suitably  equipped  hygienic 
laboratories  exist  in  small  number  in  this  country.  This,  of  course,  is  to  be 
very  much  regretted,  and  it  is  to  be  hoped  that  the  influence  of  this  Associ- 
ation may  be  such  as  to  lead  to  a  greater  appreciation  of  the  need  of  such 
laboratories  in  connection  with  our  teaching  bodies,  because  I  think  that  such 
hygienic  laboratories  in  connection  with  universities  should  work  out  prob- 
lems that  are  different  from  those  which  interest  municipal  and  state  boards 
of  health. 

Let  us  consider  for  a  moment  some  of  the  results  obtained  from  such  lab- 
oratories. As  you  all  know,  one  of  their  main  purposes  is  to  assist  physicians 
in  making  exact  diagnoses  of  certain  diseases.  Their  greatest  triumphs  are 
in  relation  to  diphtheria,  in  the  recognition  of  the  cases  of  genuine  diph- 
theria, on  the  one  hand,  and  in  seeing  to  it  that  specific  treatment  by  anti- 
toxin is  properly  carried  out.  But  their  field  of  usefulness  is  by  no  means 
limited  to  diphtheria,  but  extends  to  the  diagnosis  of  other  diseases,  such  as 
42 


618  LABOKATORIES  AND  PUBLIC  HEALTH 

tuberculosis,  typhoid  fever  and  malaria.  While  often  tuberculosis  is  readily 
recognized  by  the  physician,  once  in  a  while  cases  occur  in  which  the  physi- 
cian must  be  in  doubt  as  to  the  diagnosis,  and  he  should  be  able  to  call  to  his 
aid  those  who  are  working  in  these  laboratories  for  the  purpose  of  enabling 
him  to  make  a  correct  diagnosis.  The  diagnosis  of  fevers,  such  as  typhoid 
and  malarial  fever,  offers  an  important  field  of  usefulness  for  these  labora- 
tories, particularly  in  the  south.  In  the  recent  war  we  are  told  that  the  diag- 
nosis of  typhoid  fever  was  made  with  great  reluctance,  and  that  physicians 
often  made  a  diagnosis  of  malarial  fever  in  many  cases  of  genuine  typhoid 
fever.  We  have  means  at  our  disposal  for  the  accurate  diagnosis  of  these  two 
diseases.  The  diagnosis  of  typhoid  fever  can  frequently  be  made  with  the 
Widal  reaction,  and  it  looks  now  as  if  there  were  to  be  other  methods  added 
which  will  enable  us  to  make  a  diagnosis  at  an  earlier  stage  of  the  disease 
than  where  the  Widal  reaction  is  applicable  or  in  cases  where  this  reaction 
fails.  Especially  to  be  desired  is  the  establishment  of  laboratories  available 
for  the  diagnosis  of  malaria  in  the  regions  where  malaria  prevails,  particu- 
larly the  severe  forms  of  the  affection.  Nothing  ishould  be  called  malaria  un- 
less the  malarial  parasite  is  present,  and  an  exact  diagnosis  of  the  disease  can 
be  made  by  samples  of  blood  properly  collected.  With  a  little  instruction  the 
physician  should  be  able  to  send  these  specimens  in  such  a  way  that  a  report 
could  be  returned  within  a  short  time  as  to  the  existence  of  malaria.  When 
we  consider  the  practical  importance  of  these  two  diseases  in  this  country, 
and  the  fact  that  typhoid  fever  is  preventable  and  that  the  recent  discoveries 
regarding  the  relation  of  the  mosquito  to  the  spread  of  malaria  offer  pros- 
pects of  eradicating  malaria,  the  importance  of  extending  in  the  direction 
indicated  the  work  of  municipal  and  state  laboratories  is  apparent. 

Then,  there  is  the  chance  of  one  of  the  greater  devastating  epidemics 
making  its  appearance.  The  municipal  and  state  boards  of  health  can  make 
early  diagnoses.  Thus  if  Asiatic  cholera  should  make  its  appearance,  effec- 
tive measures  of  prevention  can  now  be  taken  at  the  onset,  for  it  is  important 
to  recognize  the  first  case  of  the  disease  before  it  can  gain  a  foothold.  The 
experience  during  the  last  cholera  epidemic  in  Germany  was  that  when  the 
first  cases  were  recognized  and  immediate  measures  were  taken  to  check  the 
spread  of  the  disease,  those  measures  were  very  effective.  But  where  the 
disease  was  allowed  to  gain  a  foothold,  it  was  difficult  to  put  an  end  to  tlie 
epidemic.  Suppose  the  plague  should  make  its  appearance  in  this  coimtry; 
if  the  city  or  state  is  })rovided  with  a  suitable  laboratory,  with  well  trained 
physicians,  the  first  case  or  two  should  be  recognized  and  effective  measures 
of  prevention  should  be  taken,  so  that  these  laboratories  should  stand  as  an 
effective  defence  between  us  and  the  outbreak  of  this  great  pestilence.    It  is 


LABORATORIES  AND  PUBLIC  HEALTH  619 

not  clear  that  these  laboratories  can  be  so  useful  with  reference  to  the  diag- 
nosis of  yellow  fever,  because  we  have  not  exact  methods,  still  they  can  be 
helpful  in  many  directions  with  reference  to  this  disease. 

These  laboratories  can  carry  on  original  investigations  and  important 
practical  work  with  reference  to  water  supplies,  to  the  disposal  of  sewage, 
to  examinations  of  food,  of  milk,  etc.  All  of  these  are  subjects  which  properly 
pertain  to  some  aspects  of  the  work  of  laboratories,  but  I  shall  not  attempt  to 
consider  them  now.  The  foundation  of  such  laboratories  has  had  a  very  im- 
portant stimulating  influence  upon  boards  of  health,  both  local  and  state. 
It  has  introduced  a  scientific  spirit  into  the  work ;  it  has  brought  into  con- 
nection with  executive  officers  the  younger  men  who  are  full  of  enthusiasm 
with  reference  to  studies  along  these  lines,  and  I  think  that  we  may  say  that 
the  general  tone  of  boards  of  health  has  been  elevated  and  stimulated  by  the 
foundation  of  laboratories  of  this  character. 

It  is  to  be  deplored  that  our  National  Government  has  had  so  little  share 
in  this  important  movement  in  public  hygiene.  This  Association  has  advo- 
cated a  plan  by  which  the  various  states  may  secure  aid  from  the  National 
Government  for  the  support  of  public  laboratories  of  hygiene  analogous  to 
that  in  operation  in  the  case  of  Agricultural  Experiment  Stations,  and  it 
seems  to  me  very  desirable  that  this  or  some  similar  plan  should  be  adopted. 
Then  we  are  all  agreed  that  our  government  should  have  a  central  sanitary 
organization  in  connection  with  which  a  laboratory  of  public  hygiene  should 
be  established.  We  can  now  appeal  as  never  before  to  the  furtherance  there- 
by of  commercial  interests,  a  motive  which  seems  to  be  more  efficacious  with 
our  legislators  than  the  lives  and  health  of  human  beings,  possibly  even  more 
than  the  welfare  of  cattle. 

Many  of  you  know  that  the  workers  in  these  laboratories  have  come  to- 
gether on  this  occasion  in  unusual  numbers,  largely  through  the  very  excel- 
lent work  of  our  public-spirited  member.  Dr.  Wyatt  Johnston.  These 
workers  have  been  brought  together  here  with  a  view  to  organizing  a  Labora- 
tory Committee  or  Section  of  this  Association.  A  few  years  ago  a  somewhat 
similar  meeting  of  bacteriologists  was  held  under  the  auspices  of  the  Water 
Committee  of  this  Association  in  New  York,  and  we  all  felt  at  that  time  that 
it  would  be  fortunate  if  we  could  have  a  permanent  organization  composed 
of  such  men  as  were  there  assembled.  In  fact,  the  idea  of  organizing  the 
working  bacteriologists  and  allied  chemists  into  a  biochemical  section  has 
been  in  the  air  for  some  time,  and  the  outcome  seems  to  be  the  best  form  of 
organization,  viz. :  one  which  will  bring  these  experts  into  this  Association. 
What  we  propose  to  do  is  to  bring  them  as  a  group  here  and  have  them 
become  members  of  the  Association.     There  are  many  questions  which  are 


620  LABORATORIES  AXD  PUBLIC  HEALTH 

very  technical,  relating  to  methods  of  procedure,  etc.,  which  it  would  not  be 
at  all  appropriate  to  bring  before  the  general  body  of  the  Association,  such 
as  chemical  examinations  of  water,  classification  of  water  bacteria,  etc.,  etc. 
It  is  proposed,  therefore,  that  this  relatively  small  group  of  members  of  this 
Association  shall  constitute  a  sub-group — call  it  what  you  like.  I  do  not 
think  Laboratory  Committee  is  a  designative  term,  in  that  it  does  not  express 
exactly  the  scope  of  the  work.  However,  matters  of  detail  can  be  readily 
settled  by  a  conference  committee.  The  idea  is  that  we  should  be  called  a 
section  of  this  Association,  which  shall  assemble  here  at  the  same  time  that 
the  general  Association  comes  together,  but  that  the  meetings  of  the  smaller 
body  or  section  shall  take  place  on  the  day  preceding  the  meeting  of  the 
general  Association,  and,  if  possible,  their  special  work  should  be  completed 
then.  If  any  work  remains  over,  provision  should  be  made  for  finishing 
it  without  conflicting  with  the  sessions  of  the  general  body.  Subjects  of 
special  interest  only  to  the  practical  worker  should  be  discussed  before  the 
meeting  of  the  section,  and  members  of  this  section  having  papers  of  general 
interest  should  present  them  before  the  Association.  The  details  of  organ- 
izing such  a  section  can  be  worked  out  later.  It  is  clear  to  us,  however,  that 
none  should  be  eligible  to  membership  in  the  section  who  do  not  become  like- 
wise members  of  the  American  Public  Health  Association.  That  is  our 
understanding,  and  we  ask  no  special  autonomy  other  than  that  we  shall 
come  together  in  connection  with  your  meeting  by  such  an  arrangement  as 
will  be  mutually  advantageous,  increasing  your  membership  in  quantity  and 
quality,  bringing  certain  kinds  of  members  whom,  I  am  sure,  you  will  all  be 
glad  to  welcome  here  to  add  to  the  usefulness  of  the  Association.  It  will  be 
of  advantage  to  bacteriologists  to  come  into  close  contact  with  the  practical 
work  of  this  Association,  and  to  this  Association  to  receive  these  workers. 


DUTIES  OF  A  HOSPITAL  TO    THE    PUBLIC   HEALTH ' 

It  is  a  well  known  fact  that  there  are  no  social,  no  industrial,  no  economic 
problems  which  are  not  related  to  problems  of  health.  The  better  conditions 
of  living,  housing,  working  conditions  in  factories,  pure  food,  a  better  supply 
of  drinking  water,  all  these  great  questions,  social,  industrial  and  economic, 
are  hound  up  with  the  problems  of  public  health.  The  humanitarian  move- 
ment has  been  one  of  the  great  agencies  in  promoting  the  better  health  move- 
ment. There  have  been  two  great  means  by  which  interest  in  public  health 
and  the  movement  for  the  promotion  of  the  health  of  the  community  have 
been  advanced.  One  has  been  the  new  humanity,  the  other  has  been  tlie 
advance  in  knowledge.  I  regret  to  say  that  I  believe  the  impulse  has  been 
stronger,  on  the  whole,  from  those  interested  in  the  humanitarian  movement 
than  it  has  been  from  my  own  profession.  Anyone  who  is  informed  as  to 
tlie  influences  which  are  operative  in  the  last  century,  from  1830  to  1850, 
which  initiated  the  modern  public  health  movement  and  culminated  in  the 
passage  of  the  public  health  act  in  1848  in  England,  knows  that  it  was  less 
a  movement  on  the  part  of  the  medical  profession  than  it  was  on  the  part 
of  philanthropists.  Those  interested  in  the  conditions  of  the  laboring 
classes  and  informed  as  to  the  steps  taken  for  the  prevention  of  disease,  know 
that  it  was  the  human  impulse  more  than  any  other  which  started  the  modern 
public  health  movement — at  lea,?t,  the  governmental  activities,  and  the 
recognition  that  the  care  of  the  health  of  the  people  is  an  important  func- 
tion of  government. 

But,  after  all,  that  impulse  alone  would  not  have  been  sufficient.  It  is  of 
vital  importance  that  health  activities  should  be  based  upon  accurate  knowl- 
edge of  the  cause  and  of  the  spread  of  disease.  At  the  period  (1848)  of 
which  I  am  speaking,  they  knew  little  about  how  such  diseases  as  typhoid 
fever  and  cholera  were  spread.  Public  hygiene  was  a  blundering  affair  then. 
Efforts  costing  vast  sums  of  money  v*ere  misdirected  and  wasted.  However, 
one  idea  dominated  at  that  time,  which  was  in  many  ways  a  fortunate  one 
at  that  stage;  this  idea  was  the  relation  of  disease  to  conditions  of  filth.  It 
was  known  that  one  disease,  typhus  fever,  especially  bore  a  relation  to  filth, 
and  through  the  application  of  this  knowledge  typhus  fever  was  checked. 

'  Report  of  an  address  delivered  before  the  National  Conference  of  Charities 
and  Correction,  Baltimore,  May  14,  1915. 

Proc.  Nat.  Confer.  Char.,  Bait.,  1915,  209-218. 

621 


622  HOSPITAL  AND  PUBLIC  HEALTH 

Until  its  recent  appearance  in  eastern  Europe  typhus  fever  was  practically 
exterminated  from  civilized  countries.  But  the  new  knowledge  came  with 
the  discover}'  of  the  causation  of  the  class  of  disease  of  the  greatest  signifi- 
cance to  mankind,  the  infectious  diseases. 

We  could  have  no  more  striking  example  of  the  health-saving,  the  life- 
saving  knowledge  which  comes  from  penetration  into  the  cause  of  disease, 
deeper  insight  into  the  manner  in  which  disease  is  spread,  than  the  vast 
benefits  which  have  come  from  the  discoveries  of  Pasteur  and  Koch  and 
the  work  carried  on  ])y  them  and  those  following  them.  These  discoveries 
initiated  a  movement  in  medicine  which  gave  a  new  face  to  things,  so  that 
we  think  of  modern  medicine  as  something  quite  different  from  the  medi- 
cine of  the  past.  We  think  of  it  often  as  being  more  different  than  we  are 
justified  in  doing.  The  truth  is  that  there  has  been  no  change  in  the  real 
aims  of  medicine  from  the  beginning.  From  the  days  of  antiquity,  the 
aim  of  the  physician  has  always  been  to  cure  and  to  prevent  disease.  It  is 
precisely  that  consistency  of  purpose  which  gives  such  interest  to  the 
future  of  medicine,  no  matter  how  futile  the  efforts  of  the  past  may  have 
been  nor  how  long  men  wandered  in  ignorance  and  darkness. 

But  there  came  to  us  a  new  light,  and  with  it  a  new  power.  The  physi- 
cian acquired  a  control  over  the  spread  of  many  of  the  infectious  diseases 
and  in  the  case  of  some  a  new  power  in  the  treatment  of  disease  which 
rendered  his  mission  a  far  more  significant  one  for  the  world  than  it  had 
ever  been  before.  It  is  now  possible  to  control  great  pestilences.  We  be- 
lieve even  in  the  possibility  of  the  complete  eradication  of  such  pestilences. 
Only  the  other  day  I  attended  a  conference  in  New  York  where  the  possi- 
bility of  taking  up  the  complete  extermination  of  yellow  fever  was  considered. 
It  is  possible  that  will  be  initiated.  Anyway,  the  problem  seems  a  soluble 
one,  and  the  work  undertaken  in  that  direction  full  of  promise.  This  advance 
in  medicine  was  not  merely  in  relation  to  this  class  of  diseases  but  it  affected 
all  branches  of  medicine.  It  stimulated  investigation,  so  that  the  physician 
can  do  far  more  in  all  classes  of  diseases  than  was  possible  in  the  past.  There- 
fore medicine  makes  an  appeal  to  the  community,  it  makes  an  appeal  to  the 
government,  for  support,  it  makes  an  appeal  to  public  spirited  philan- 
thropists, wliich  it  never  could  have  done  in  the  past.  Far-sighted,  public 
spirited  philanthropists  who  appreciate  the  possibilities  of  further  explora- 
tion in  this  field  have  enabled  medicine  to  undertake  investigations,  and  it 
is  above  all  important  that  we  should  acquire  further  knowledge  as  to  the 
causation  of  disease. 

I  have  no  doubt  that  we  are  today  directing  our  efforts  in  the  wrong  way, 
as  I  have  said  they  wore  doing  sixty  and  seventy  years  ago.  I  have  no  doubt 
we  are  spending  millions  of  money  fruitlessly,  wastefully,  as  com^jared  with 


HOSPITAL  AND  PUBLIC  HEALTH  633 

what  the  possibilities  might  be  if  we  had  a  more  exact  knowledge  of  the 
causation  and  propagation  of  disease.  Consider  for  a  moment  the  vast  sums 
formerly  wasted  in  efforts  to  control  yellow  fever  by  quarantine,  and  how 
simple  the  problem  became  when  we  learned  that  yellow  fever  can  be  spread 
only  in  one  way,  by  the  bite  of  a  particular  species  of  mosquito. 

There  are  a  great  variety  of  agencies  concerned  in  the  promotion  of  public 
health,  prevention  of  disease,  and  the  treatment  of  disease,  AVhile  the  theme 
assigned  to  me  relates  to  one  particular  agency  in  this  warfare  upon  disease — 
the  hospital — I  must  say  at  least  a  word  about  two  others  of  most  importance, 
namely,  the  governmental  agencies,  public  health  boards,  commissioners  and 
officials,  simply  to  emphasize  the  importance  of  better  organization  and  bet- 
ter support  of  our  public  health  officials  and  boards.  Among  our  chief 
needs  I  would  mention,  in  the  first  place,  larger  appropriations;  in  the 
second  place,  better  trained  experts ;  and,  in  the  third  place,  taking  the  work 
out  of  politics.  I  am  not  going  to  elaborate  on  these,  but  I  hardly  like  to 
speak  before  an  audience  of  this  kind  without  at  least  referring  to  the  im- 
portance of  better  support  and  organization  of  our  boards  of  health,  and  the 
great  need  of  opportunities  for  the  better  training  of  experts  in  that  field. 
The  selection  of  a  commissioner  of  health  is  of  course,  a  matter  in  which 
the  whole  community  is  interested.  The  entire  country  should  be  looked 
over  in  order  to  find  the  best  man  for  the  position — not  simply  the  one  who 
can  easily  be  found  in  the  community. 

One  other  agency  I  should  at  least  like  to  refer  to,  and  that  is  the  public 
health  nurse.  One  of  the  contributions  of  the  hospital  to  public  health  work 
has  been  the  trained  nurse.  We  are  familiar  with  the  incalculable  advan- 
tages which  come  from  the  introduction  of  the  system  of  visiting  nurses. 
They  should  be  extended  into  larger  use  and  there  should  be  a  more  special- 
ized training  for  the  public  health  nurse.  It  is  of  the  greatest  importance 
that  her  activities  should  extend  to  the  rural  districts.  One  of  the  strikino- 
circumstances  of  the  modern  public  health  movement  is  the  limited  advantage 
which  rural  communities  have  derived  from  this  new  knowledge. 

As  regards  the  relation  of  the  hospital  to  health,  there  is  no  activity  of 
the  hospital  that  is  not  related  to  health  directly  or  indirectly.  I  shall  speak 
somewhat  disconnectedly  on  certain  points,  I  think,  because  it  is  quite  im- 
practicable in  the  time  available  to  present  the  subject  in  a  comprehensive 
and  systematic  manner.  First,  as  regards  certain  types  of  hospitals.  We 
have  the  general  hospital  and  various  kinds  of  special  hospitals.  There  is 
one  of  these  special  hospitals,  the  tuberculosis  hospital,  which  has  had  such 
influence  and  which  brings  so  important  lessons  that  I  would  like  to  refer 
to  it.  I  do  not  propose  to  discuss  the  importance  of  the  hospital  in  the  tuber- 
culosis crusade,  as  that  would  lead  too  far.    Suffice  it  to  say  that  it  has  the 


624  HOSPITAL  AND  PUBLIC  HEALTH 

very  first  place.  The  tuberculosis  hospital  has  two  functions  which  it  is 
important  to  bear  in  mind.  One  is  the  educational  function.  The  benefit 
of  residence  in  a  tuberculosis  hospital  to  a  consumptive  is  not  measured 
solely  by  improvement  in  his  health.  So  far  as  the  community  is  concerned, 
it  is  measured  also  by  the  education  of  the  patient  in  methods  of  right  living. 
There  has  probably  been  no  influence  which  has  had  larger  eifect  in  stirring 
up  the  public  mind  as  regards  many  of  the  problems  of  the  public  health 
than  the  tuberculosis  crusade.  It  has  taught  people  the  value  of  fresh  air; 
it  has  emphasized  the  importance  of  proper  conditions  in  the  household  and 
in  the  factory,  because  tuberculosis  is  a  disease  which  is  spread  by  the  imme- 
diate environment — in  houses,  workshops  or  factories.  The  lessons  which 
have  reached  the  public,  largely  through  the  work  of  our  tuberculosis  hospi- 
tals and  sanatoria,  have  been  of  inestimable  value  in  their  effects  upon  public 
health. 

I  would  like  to  point  out  in  this  connection,  familiar  as  it  is,  that  just  as 
in  the  case  of  tuberculosis,  so  in  nearly  all  the  efforts  to  control  infectious 
diseases  there  are  incidental  benefits  which  are  often  not  foreseen  but  which 
in  many  instances  equal,  if  not  exceed,  the  actual  effect  upon  the  control 
of  the  particular  disease  in  question.  Take,  for  instance,  the  control  of 
typhoid  fever,  with  the  consequent  insistence  upon  a  pure  water  supply, 
pure  food,  and  certain  conditions  relating  to  the  spread  of  disease  from 
person  to  person,  using  the  military  to  clean  up  unsanitary  morasses  and 
Bwamps  around  human  habitations  and  rendering  large  areas  fertile  and 
suitable  for  cultivation.  One  might  go  on  and  point  out  benefits  often  far  in 
excess  of  the  actual  results  which  are  immediately  in  view  when  the  attack 
is  first  made. 

The  tuberculosis  dispensary  is  something  very  different  from  the  ordinary 
dispensary.  It  is  perfectly  obvious  that  it  would  be  absurd  to  conduct  a 
tuberculosis  dispensary  as  most  dispensaries  were  conducted  before  the  great 
movement  initiated  by  our  chairman,  Dr.  Cabot,  came  into  use,  by  having 
the  patient  simply  come  to  the  dispensary,  receive  a  dose  of  medicine,  and 
then  go  away.  The  idea  of  following  the  patient  to  the  home,  of  instruction 
in  the  home,  not  only  of  the  patient  but  of  all  in  proximity  to  him — all  that 
conception,  which,  thanks  to  Dr.  Cabot,  is  now  so  familiar  in  the  work  of  a 
dispensary,  although  so  imperfectly  attained  in  many  cases — is  exemplified 
in  a  striking  way  by  the  tuberculosis  dispensary. 

There  are  many  other  special  hospitals  for  the  eye,  ear,  throat,  and  child- 
ren's diseases.  I  have  only  one  remark  to  make  in  regard  to  these.  It  is  a 
pity  that  these  hospitals  have  developed  to  such  a  large  extent  as  independent, 
detached  hospitals,  often  unsuitably  located,  and  out  of  touch  with  the 
general  hospital  movement.    I  cannot  pause  to  consider  why  this  has  been. 


HOSPITAL  AND  PUBLIC  HEALTH  625 

It  is  mainly  because  the  movement  started  about  a  century  ago  and  became 
active  about  sixty  or  seventy  years  ago,  and  those  who  were  interested  in  these 
branches  were  not  welcome  in  general  hospitals  and  were  more  or  less  com- 
pelled to  go  to  one  side  to  establish  these  special  institutions.  It  is  un- 
fortunate, and  it  is  very  important  that  in  future  we  should  do  all  we  can  to 
remedy  this  condition,  and  when  a  new  hospital  of  this  kind  is  founded  it  is 
probable  that  it  should  be  in  connection  with  a  general  hospital.  Referring 
to  the  three  special  hospitals  we  have  been  so  fortunate  as  to  secure  in  con- 
nection with  the  Johns  Hopkins  Hospital,  they  are  far  more  useful  institu- ' 
tions  and  do  a  far  larger  service  to  the  community  by  virtue  of  the  fact  that 
they  are  on  the  grounds  of  the  hospital  and  in  intimate  association  with  the 
Johns  Hopkins  Hospital — in  fact,  administered  by  that  hospital. 

I  cannot  pause  to  discuss  tlie  development  of  the  modem  hospital,  but  it 
is  something  very  different  from  the  hospital  of  the  old  days.  One  of  the 
most  significant  developments  in  medicine,  and  therefore  in  public  health, 
has  been  the  development  of  the  modern  general  hospital.  This  has  come 
about  largely  through  increased  knowledge  of  the  methods  of  study  and 
diasniosis  and  treatment  of  disease.  It  has  come  about  also  to  some  extent 
through  a  more  correct  view  as  to  the  function  of  the  hospital  in  education 
and  in  the  treatment  of  patients.  These  new  conceptions  are  responsible 
for  a  situation  where  the  patient  profits  by  the  resources  of  modern  medicine 
and  of  education  in  sanitary  ways  of  living  to  an  extent  quite  impossible  in 
private  practice.  The  best  that  can  be  done  with  existing  knowledge  for  the 
treatment  and  relief  of  disease  is  to  be  found  now  in  the  w^ell  equipped  and 
well  organized  general  hospital. 

For  whom  are  these  benefits  available?  In  all  the  American  hospitals 
where  the  rich  and  the  poor  are  both  admitted  they  are  available  for  the 
very  rich  and  the  very  poor.  On  the  whole  I  think  the  poor  derive  the  great- 
est advantage.  The  rich  formerly  did  so,  and  still,  I  think,  to  a  considerable 
extent,  share  the  opportunities  of  medical  discoveries  in  the  treatment  of 
their  diseases.  But  there  is  a  large  middle  class  which  at  present  is  not 
adequately  provided  for.  I  see  that  that  is  a  subject  for  a  paper  in  the  pro- 
gram of  the  Conference.  I  was  not  fortunate  enough  to  hear  the  paper,  but 
the  very  title  shows  an  appreciation  of  the  situation.  One  of  the  urgent 
needs  is  to  supply  adequate  accommodations  in  the  best  of  our  general 
hospitals  for  all  classes  of  the  community.  Whether  they  shall  be  provided 
for  in  inexpensive  private  rooms  or  whether  by  more  attractive  arrange- 
ment in  public  wards,  so  as  to  make  the  accommodation  more  acceptable, 
I  am  not  prepared  to  say.  Although  I  am  talking  on  these  subjects,  I  am  not 
a  hospital  physician  and  am  not  in  practice  and  have  not  that  intimate 
personal  contact  with  the  .subject  that  would  make  my  opinion  as  to  the 
best  solution  of  a  problem  of  this  character  of  particular  value. 


626  HOSPITAL  AND  PUBLIC  HEALTH 

Why  is  it  that  hospitals  offer  these  superior  advantages  in  the  treatment 
and  care  of  disease  ?  It  is  because  they  are  well  equipped  and  organized  and 
because  there  is  a  whole  staff  of  assistants.  The  study  of  modern  disease  re- 
quires all  sorts  of  examinations  by  new  methods  that  are  in  many  cases 
intricate.  Sometimes  it  is  doubtful  whether  the  knowledge  so  derived  is 
applicable  to  the  case  in  hand,  but  whatever  sheds  light  upon  the  extent  and 
character  of  disease  must  eventually  be  found  of  advantage  to  the  patient. 
In  many  cases  the  private  physician  is  enabled  to  bring  to  bear  upon  his 
patient  all  of  these  resources  essential  to  the  accurate  diagnosis  and  treat- 
ment of  disease.  The  hospital  reaches  only  a  relatively  small  fraction  of 
the  entire  community — I  do  not  know  how  many.  It  has  been  said  that  not 
more  than  one-tenth  of  the  sick  are  cared  for  in  hospitals.  The  opportunities 
are  inadequate  at  present  for  meeting  this  great  need.  It  is  possible  that  the 
private  physicians  may  be  enabled  in  some  way  or  other  to  have  at  their 
disposal  such  advantages  as  exist  at  present  almost  solely  in  hospitals. 

Some  think  that  the  solution  is  going  to  be  the  eventual  disappearance  of 
the  private  practitioner  as  we  know  him  today.  Some  think  the  profession 
is  to  be  socialized.  Stei>s  in  that  direction  have  already  been  taken  in  Den- 
mark and  other  Scandinavian  countries  where  the  doctors  are  paid  by  the 
Btate,  and  it  is  interesting  to  learn  the  results  of  those  experiences.  But  I 
think  it  would  be  a  pity  to  have  the  whole  practice  of  medicine  institution- 
alized. There  was  something  so  fine  about  the  best  type  of  family  doctor 
in  the  old  days.  My  father  was  a  country  doctor  and  I  know  something  of 
the  life  and  what  it  meant  to  patients  so  tliat  I  cannot  help  feeling  that  every 
effort  ought  to  be  made  to  rescue  this  situation.  A  recognition  of  it  is,  of 
course,  the  first  step.  How  it  is  to  be  met  I  do  not  know.  I  have  read  that  in 
Fall  Eiver  the  physicians  have  arranged  for  coordinated  effort  in  their  labora- 
tories which  results  in  conditions  similar  to  those  wliich  exist  in  hospitals. 
I  desire  to  call  your  attention  to  the  situation  without  attempting  myself 
to  suggest  a  solution ;  but  there  is  this  contrast  today  as  between  the  organ- 
ized, well  equipped  hospital  and  the  opportunities  there  afforded  for  the 
treatment  of  disease,  and  the  situation  in  private  practice.  As  regards  the 
services  rendered  by  the  hospital,  the  side  of  it  with  which  I  am  most  familiar 
is  the  educational  one.  The  primary  purpose — and  it  must  remain  the 
primary  purpose,  is  the  care  of  the  patient.  Nothing  can  be  done  in  a  hospi- 
tal which  in  any  way  can  be  of  possible  injury  to  the  patient.  The  argument 
is  so  familiar  that  perhaps  it  hardly  needs  presentation,  that  the  use  of  the 
hospital  for  educational  purposes  really  is  for  the  benefit  of  the  patient.  If 
this  can  be  demonstrated,  then  we  shall  be  convinced  that  a  hospital  which 
Berves  not  merely  a  humanitarian  purpose,  but  educational  and  scientific 
purposes  as  well,  is  doing  a  far  more  important  and  larger  work  than  the 


HOSPITAL  AND  PUBLIC  HEALTH  627 

hospital  which  has  nothing  more  to  do  than  to  care  for  the  patient.  We  must 
bring  this  to  the  attention  of  the  public  at  every  suitable  opportunity. 

The  medical  school  and  hospital  in  the  past  have  developed  abroad  sepa- 
rately, and  the  real  problems  of  medical  education  in  this  country  are  the 
result  of  that  divergent  development.  We  know  now  that  it  is  important 
to  bring  them  together.  They  never  should  have  developed  apart.  But  the 
difficulties  are  greater  than  one  might  imagine.  The  medical  school  must 
have  satisfactory  relations  to  a  hospital.  It  is  fortunate  if  the  university 
or  medical  school  has  its  hospital,  as  we  have  at  the  Johns  Hopkins.  But 
as  the  future  of  medical  education  really  depends  upon  its  connection  with 
a  hospital,  I  should  consider  the  future  of  medical  education  dark  indeed, 
in  this  country,  if  we  were  to  build  hospitals  without  the  university  assum- 
ing the  administration  of  them.  The  important  thing  is  for  the  trustees  of 
privately  endowed  institutions  to  feel  that  they  are  doing  the  best  for  the 
hospital  in  making  it  freely  available  for  medical  teaching.  This  superior 
kind  of  hospital  is  to  a  large  extent  at  present  in  this  country  the  well  en- 
dowed private  hospital,  but  our  municipal  and  state-supported  hospitals  are 
beginning  to  awake.  It  is  important,  and  it  is  a  requirement  of  modern 
sanitation,  that  these  facilities  should  be  supplied.  When  I  speak  of  the 
educational  side  of  the  hospital,  I  have  in  mind  not  merely  opportunities  for 
training  doctors  and  nurses,  but  for  the  training  of  patients  as  well.  Take, 
for  example,  the  movement  for  the  early  recognition  of  cancer — the  impor- 
tance of  the  public  being  instructed  that  sores  that  do  not  heal  up  should 
have  the  physician's  attention,  that  early  operation  for  cancer  is  usually 
successful  and  the  results  of  delay  lamentable — the  result  of  which  has  been 
an  organized  effort  to  bring  this  knowledge  home.  Do  we  make  use  of  our 
knowledge  as  we  should  with  patients  coming  to  the  dispensary?  There  are 
the  same  opportunities  for  bringing  lessons  home  as  to  right  conditions  of 
living,  health,  and  prevention  of  disease  as  are  exemplified  in  the  case  of 
tuberculosis. 

There  is  the  scientific  work  of  a  hospital.  Definite  knowledge,  of  course, 
is  the  most  obvious  result  of  the  work  of  those  engaged  in  hospital  activities, 
but  the  spirit  of  investigation  has  a  value  so  great  for  the  workers  that  I  do 
not  believe  it  can  be  overestimated.  It  is  incumbent  upon  mimicipal  and 
state-supported  hospitals  to  make  provision  whereby  the  staff,  especially  the 
young  men,  may  be  stimulated  by  laboratory  opportunities.  The  equipment 
can  be  relatively  modest,  but  there  should  be  opportunities  which  make  them 
see  that  medicine  is  something  more  than  a  trade.  I  would  emphasize  that 
the  value  of  the  investigating  spirit  is  not  to  be  measured  by  making  dis- 
coveries in  science.  The  spirit  of  investigation  is  a  stimulus  to  a  real  pleas- 
ure in  work,  to  better  work  and  better  care  of  patients,  and  unless  the  workers 
have  it,  their  task  becomes  merely  routine. 


628  HOSPITAL  AND  PUBLIC  HEALTH 

I  want  to  say  a  word  about  autopsies.  Postmortem  examination  is  not 
my  theme,  but  it  is  through  the  knowledge  derived  from  them  that  many  of 
the  great  advances  in  medicine  have  come.  There  is  every  reason  why  they 
should  be  characterized  as  a  matter  of  routine.  Dr.  Brookings,  who  has 
done  so  much  at  the  Washington  University  Medical  School  has  said :  "  I 
would  not  care  to  put  myself  in  the  hands  of  a  physician  who,  if  I  should  die, 
did  not  want  an  autopsy  and  did  not  want  to  face  the  results.'*  The  matter 
is  of  sufficient  importance,  I  tliink,  to  bring  to  the  attention  of  an  audience 
of  this  character. 

I  have  only  touched  here  and  there  upon  my  subject.  In  conclusion,  I 
would  like  to  add  just  one  thought.  It  is  of  the  utmost  importance  that 
hospitals  should  be  more  linked  together  with  all  the  agencies  which  are  con- 
cerned with  public  health  work.  Dr.  Cabot  has  done  immense  service  in 
waking  us  up  on  the  question  of  dispensaries.  It  is  a  wonder  we  could  have 
slept  so  long.  The  new  era  that  has  been  ushered  in  by  social  service  work 
is  certain  to  see  the  dispensary  brought  into  closer  relations  with  other 
agencies  concerned  in  all  its  fields  of  activity.  I  think  there  is  room  for  a 
better  organization,  a  better  coordination,  a  more  effective  cooperation  of  the 
hospital  with  the  boards  of  health.  I  happen  to  be  a  member  of  a  state 
board  of  health,  and  know  that  we  see  ways  in  which  the  hospitals  could  be 
more  cooperative  than  they  are  at  present  with  all  kinds  of  charity  and  relief 
organizations.  The  hospitals  that  take  this  form  are  to  be,  not  the  only 
agency,  but  I  think  a  primary  one  in  the  promotion  of  public  health. 


OPENING  REMARKS  BY  THE  PRESIDENT  OF  THE  SECTION  ON 
PATHOLOGY  AND  BACTERIOLOGY  OF  TUBERCULOSIS ' 

I  esteem  it  a  high  honor  and  privilege  in  behalf  of  my  American  colleagues 
to  extend  a  most  cordial  welcome  to  all  in  attendance  upon  this  first  section 
of  the  Sixth  International  Congress  on  Tuberculosis,  and  especially  to  those 
who  have  come  from  foreign  countries  to  participate  in  our  proceedings.  We 
are  indeed  fortunate  in  the  presence  of  so  many  distinguished  investigators 
whose  papers  and  discussions  enrich  our  program  and  give  assurance  that 
this  Congress  will  not  pass  without  substantial  contributions  to  our  knowl- 
edge of  tuberculosis. 

It  will  not  be  deemed  invidious  if  I  express  the  special  gratification  which 
we  all  feel  in  having  with  us,  as  an  active  participant  in  the  work  of  this 
Section,  his  Excellency,  Professor  Koch,  the  illustrious  discoverer  of  the 
tubercle  bacillus,  who  must  rejoice  to  witness,  in  such  a  gathering  as  this, 
the  evidences  of  the  far-reaching  and  inestimable  benefits  to  mankind  which 
have  come  from  this  discovery,  and  the  promise  of  greater  benefits  in  store. 
We  appreciate  most  highly  the  participation  of  so  many  eminent  colleagues 
from  France,  who  have  cooperated  so  generously  and  so  effectively  in  our 
efforts  toward  the  success  of  this  Congress.  We  welcome  warmly  our  kindred 
in  speech  and  in  blood  from  Great  Britain  and  her  possessions  and  with  equal 
cordiality  our  fellow-workers  from  Germany  and  Austria-Hungary,  from 
Holland  and  the  Scandinavian  countries,  from  Spain,  Russia  and  other 
European  countries,  from  Japan  and  the  Orient,  and  from  our  sister  repub- 
lics of  Central  and  South  America. 

Every  effort  has  been  made  to  assure  the  truly  international  character  of 
this  Congress,  and  a  glance  at  our  program  will  indicate  that  this  result  has 
been  secured.  Over  seventy  per  cent  of  the  papers  on  the  program  of  Section 
I  are  contributed  by  participants  from  foreign  countries — a  gratifying  re- 
sult made  possible  by  a  certain  measure  of  self-restraint  on  the  part  of 
American  workers,  who  are  prepared  to  furnish  papers,  if  the  time  permitted. 

A  word  concerning  the  construction  of  the  program  of  this  Section  may  be 
of  interest.  After  consultation  with  other  officers  of  the  Section  I  determined 
that,  instead  of  selecting  themes  for  discussion  and  inviting  referees  and 

*  Remarks  made  before  the  First  Section  of  the  Sixth  International  Congress 
of  Tuberculosis,  Washington,  D.  C,  September  28,  1908. 

Tr.  VI  Internat.  Cong.  Tuberc,  Phila.,  1908,  I,  Sect.  I,  2-4. 

629 


630  OPENING  REMARKS 

co-referees  in  accordauce  with  the  usual  custom,  I  would  accept  papers 
voluntarily  submitted  and  then  arrange  them  in  groups  with  the  expecta- 
tion that  the  result  would  be  much  the  same,  and  that  the  more  important 
and  larger  themes  would  thus  be  presented  by  those  actually  engaged  in 
their  study  and  whose  interest  was  for  the  time  concentrated  upon  the  sub- 
jects presented  by  tliem.  By  thus  grouping  the  titles  of  papers  voluntarily 
submitted,  the  larger  topics,  such  as  the  biology  and  chemistry  of  the  tubercle 
bacillus,  the  channels  and  sources  of  infection,  the  specific  tuberculin  reac- 
tions, immunity,  the  relations  of  hmnan  and  bovine  tuberculosis,  will  be 
presented  in  a  satisfactory  and  authoritative  manner. 

In  view  of  the  crowded  condition  of  our  program  I  must  remind  the 
readers  and  discussers  of  the  necessity  of  strict  enforcement  of  the  rules, 
that  the  time  allotted  for  referees  and  co-referees  is  not  to  exceed  fifteen 
minutes,  for  readers  of  papers  ten  minutes,  and  for  participants  in  the  dis- 
cussions five  minutes ;  and  especially  I  would  urge  the  importance  of  handing 
to  the  Secretary  of  the  Section  the  written  remarks  in  discussion  before  the 
close  of  each  meeting  in  order  to  secure  their  appearance  in  the  "  Transac- 
tions." 

The  main  significance  of  the  International  Congresses  of  Tuberculosis 
has  been  in  the  past,  and  will  continue  to  be,  on  the  side  of  prevention  of  the 
disease.  As  has  been  said,  tuberculosis  is  indeed  the  disease  of  the  people, 
in  a  truer  and  larger  sense  than  can  be  affirmed  of  any  other  malady.  From 
the  discovery  of  the  tubercle  bacillus,  and  the  study  of  its  properties,  and  of 
the  sources  and  modes  of  infection,  there  has  come  a  new  message  of  hope  to 
suffering  humanity,  so  full  of  untold  bles^sing  that  the  peoples  of  the  earth 
have  been  aroused  to  its  significance,  and  in  all  civilized  countries  there  has 
been  inaugurated  what  is  appropriately  called  the  crusade  against  tubercu- 
losis. Already  in  certain  places  the  application  of  intelligent  measures  of 
prevention,  based  upon  a  new  knowledge,  has  achieved  results  so  full  of 
promise  that  the  hopes  of  even  the  most  enthusiastic  no  longer  seem  so 
extravagant  as  they  may  once  have  appeared.  Nowhere  has  the  existing 
knowledge  been  applied  to  the  prevention  of  tuberculosis  save  in  part  and 
inadequately,  but  the  achievements  of  even  this  imperfect  application  are 
sufficient  to  inspire  the  world  to  the  search  for  fuller  knowledge,  and  to 
better  directed  and  more  efficient  efforts  toward  prevention.  The  crusade 
against  tuberculosis  is  truly  a  battle  of  the  people,  by  the  people,  and  for 
the  people.  It  is  not  a  doctors'  fight  merely,  but  all  the  forces  of  society — 
economic,  social,  moral,  legislative,  administrative,  philanthropic — must  be 
enlisted  in  thi.s  contest. 

Tiie  benefit*!  to  the  community  which  result  from  success  in  the  prevention 
of  divsease  extend,  as  a  rule,  far  beyond  the  mere  control  of  the  particular 


BY  THE  PRESIDENT  OF  THE  SECTION  631 

disease  in  question,  incalculable  as  this  benefit  may  be.  As  regards  tubercu- 
losis, it  has  become  increasingly  apparent  that  successful  prevention  will  be 
attended  by  improved  conditions  of  living,  of  work,  and  of  play ;  in  a  word, 
by  a  general  social  betterment  of  the  people.  It  is  this  aspect  of  the  crusade 
which  has  very  properly  stimulated  the  interest  of  philanthropists,  social 
workers,  and  statesmen. 

When  we  contemplate  the  popular  interest  and  enthusiasm  which  have 
already  been  aroused  in  the  campaign  against  tuberculosis,  the  readiness  to 
institute  preventive  measures,  the  large  pecuniary  resources  which  are 
available,  and  the  great  expenditure  of  money  and  of  energy  already  made 
or  in  the  process  of  making,  we  must  be  impressed  with  the  importance  of 
making  sure  that  our  measures  of  prevention  are  really  based  upon  accurate 
and  full  knowledge  of  the  mode  of  spread  of  the  disease,  and  are  so  applied 
as  to  yield  the  best  results,  in  the  most  economical  way,  most  surely  and 
most  quickly.  The  campaign  must  rest  upon  a  sound  scientific  basis,  and 
must  be  conducted  along  correct  scientific  lines.  This  scientific  foundation 
is  supplied  mainly  by  the  knowledge  furnished  by  investigation  of  the  sub- 
jects represented  in  this  first  section  of  the  Congress,  namely,  the  pathology 
and  bacteriology  of  tuberculosis.  Other  sections  of  the  Congress  may  seem 
to  be  concerned  more  directly  with  the  marshalling  of  the  forces,  with  the 
conduct  of  the  assault,  with  the  stirring  of  the  martial  spirit,  and  the  appeal 
to  arms,  but  ours  is  the  division  which  must  supply  the  ammunition  and  the 
weapons  and  the  strategy  of  the  campaign. 

While  our  existing  knowledge  of  tuberculosis  already  furnishes  the  basis 
for  vigorous  and  intelligent  measures  of  prevention  against  tuberculosis,  it 
nmst  be  conceded  that  there  are  many  important  open  problems  awaiting 
further  investigation,  and  that  there  is  still  much  diversity  of  opinion  re- 
garding the  points  essential  to  the  proper  conduct  of  the  campaign.  We  may 
confidently  anticipate  that  the  proceedings  of  this  section  will  contribute 
sometliing  of  value  towards  the  elucidation  of  some  of  these  problems  and 
toward  a  closer  agreement  of  authoritative  opinion.  They  will  be,  I  trust, 
a  source  of  pleasure  and  of  profit  to  all  in  attendance. 


WHAT  MAY  BE  EXPECTED  FROM  MORE  EFFECTIVE  APPLI- 
CATION OF  PREVENTIVE  MEASURES  AGAINST 
TUBERCULOSIS" ' 

Mr.  Chairman,  Ladies  and  Gentlemen:  To  those  who  have  so  long  pleaded 
the  cause  of  public  health  in  this  country,  often,  it  seemed  to  deaf  ears,  this 
occasion  must  be  a  source  of  great  encouragement  and  inspiration.  The 
interest  manifested  by  this  large  audience,  the  presence  as  presiding  officer 
of  one  of  our  most  distinguished  citizens,  the  stirring  addresses  of  the 
Governor  and  other  speakers,  and  the  participation  of  so  many  eminent  in 
public  life,  in  philanthropic  effort,  and  in  medicine  and  sanitation,  are  indi- 
cations of  a  great  awakening  in  behalf  of  the  health  of  the  people  of  this  state. 

This  awakening  has  come  mainly  through  interest  in  that  disease  which 
may  truly  be  called  "  the  disease  of  the  people."  No  other  disease  merits 
this  designation  in  equal  measure  with  tuberculosis,  which  carries  off  one- 
third  of  those  who  die  at  a  time  of  life  which  should  be  that  of  the  greatest 
productive  energy.  The  people  have  recognized  their  true  foe  in  tubercu- 
losis, and  are  stirring  to  the  combat  throughout  the  civilized  world. 

It  may  be  asked  why  it  is  necessary  to  arouse  the  public  regarding  the 
prevention  of  tuberculosis  more  than  concerning  other  preventable  diseases. 
Many  triumphs  of  preventive  medicine  have  been  achieved  without  the  great 
upheaval  of  popular  interest.  The  necessity  of  enlisting  the  active  interest 
and  support  of  the  public  in  the  campaign  against  tuberculosis  is  due  not 
solely  to  the  extent  of  the  ravages  of  this  disease,  enormous  as  these  are,  but 
to  the  fact  that  the  prevention  of  tuberculosis  is  a  social  and  economical 
problem  as  well  as  a  medical  one,  and  that  therefore  not  only  medical  and 
sanitary  measures  but  also  other  forces  of  the  comnmnity — legislative,  ad- 
ministrative, philanthropic,  educational — must  cooperate  in  the  struggle. 
An  important  aspect  of  the  crusade  against  this  disease  is  that  success  in  the 
struggle  signifies  also  social  betterment,  enlightenment  in  ways  of  healthy 
living  and  working  and  intelligent  interest  and  education  in  individual  and 
public  hygiene  in  general. 

'  Report  of  an  address  delivered  before  a  Public  Meeting  under  the  auspices 
of  the  State  Charities  Aid  Association  in  cooperation  with  the  State  Department 
of  Health,  In  behalf  of  a  State  Campaign  for  the  Prevention  of  Tuberculosis, 
Albany.  N.  Y.,  January  27,  1908. 

Albany  M.  Ann.,  1908,  XXIX,  256-262. 
632 


MEASURES  AGAINST  TUBERCULOSIS  633 

The  thought  which  comes  first  to  my  mind,  as  I  have  witnessed  the  enthu- 
siasm and  interest  manifested  by  this  large  meeting,  is  how  such  energies 
and  forces  as  have  been  aroused  and  are  ready  to  be  moved  can  be  so 
directed  and  applied  as  to  secure  in  the  most  effective  manner  the  best 
results.  It  is  of  fundamental  importance  to  secure  the  cooperation  and  co- 
ordination of  all  the  necessary  agencies  and  to  proceed  along  well  defined, 
systematic  lines. 

Since  the  discovery  of  the  tubercle  bacillus  by  Koch  in  1882  it  has  been 
known  that  tuberculosis  is  a  preventable  disease,  and  experience  has  demon- 
strated that  in  the  initial  stage  it  is  curable  in  the  majority  of  cases.  With- 
out the  aid  of  experimentation  upon  animals  this  greatest  discovery  in  the 
domain  of  bacteriology  could  not  have  been  made. 

It  is  in  my  judgment  a  conservative  statement  that  at  least  one-half  of 
the  existing  sickness  and  mortality  from  tuberculosis  could  be  prevented 
within  the  next  two  decades  by  the  application  of  rational  and  entirely 
practicable  measures,  and  I  believe  that  we  can  look  forward  to  a  much  larger 
success.  You  can  be  assured  that  the  expenditure  of  money  and  of  well 
directed  energy  in  this  cause  will  lead  to  a  very  considerable  saving  of  human 
life,  and  that  in  no  other  direction  will  money  expended  for  sanitary  reform 
yield  equally  important  results  to  the  community. 

The  essential  elements  in  the  solution  of  the  problem  of  prevention  of 
tuberculosis  are  clear  understanding  of  the  modes  of  conveyance  of  the  dis- 
ease, well  considered,  practicable  measures  of  prevention  based  upon  this 
knowledge,  tlie  application  of  these  preventive  measures  under  the  direction 
of  skilled  sanitary  officers,  and  adequate  resources  for  their  application. 

The  justification  for  the  statement  that  the  death  rate  from  tuberculosis 
may  be  cut  in  two  is  based  upon  the  fact  that  the  saving  knowledge  which  we 
possess  regarding  this  disease  is  at  present  only  most  inadequately  and  im- 
perfectly applied  in  prevention,  and  that  even  this  inadequate  application 
has  brought  about  a  notable  decline  in  the  mortality  from  tuberculosis  in 
many  communities,  and  it  would  appear,  precisely  in  those  places  where  pre- 
ventive measures  have  been  most  effectively  employed. 

In  Prussia  the  death  rate  from  tuberculosis  has  diminished  about  forty 
per  cent  in  the  last  twenty  years.  In  Sweden  there  has  been  a  similar  reduc- 
tion. Particularly  significant  is  a  like  diminution  in  New  York  City,  which 
offers  unusually  difficult  problems  in  consequence  of  the  tenement  house 
conditions  and  the  resulting  density  of  the  population  and  of  certain  other 
unfavorable  factors.  Tlie  Health  Department  of  New  York  City,  largely 
through  the  admirable  work  of  Dr.  Biggs,  has  achieved  a  triumph  in  this 
regard  which  has  attracted  the  attention  of  sanitarians  throughout  the  world. 
43 


634  MEASUEES  AGAINST  TIIBEECULOSIS 

In  England  the  decline  in  the  death  rate  from  tuberculosis  began  long  before 
the  discovery  of  the  tubercle  bacillus  and  has  continued  to  the  present  time, 
but  in  this  country  there  have  been  throughout  this  period  special  hospitals 
for  consumptives  and  intelligent  public  sanitation. 

Permit  me  to  indicate  very  briefly  what  I  conceive  to  be  the  more  im- 
portant agencies  necessary  for  the  control  of  tuberculosis. 

1.  A  leading  role  in  the  campaign  against  any  infectious  disease  is  the 
notification  of  the  disease  to  the  health  authorities,  and  in  my  judgment 
this  should  be  recognized  as  an  essential  feature  in  the  administrative  con- 
trol of  tuberculosis.  New  York  City  deserves  the  credit  of  having  demon- 
strated the  feasibility  and  the  practical  benefits  of  the  notification  and  regis- 
tration of  tuberculosis.  In  the  light  of  this  actual  experience  of  the  workings 
of  the  system  little  weight  can  be  given  to  most  of  the  arguments  which  have 
been  and  are  still  urged  against  its  adoption,  and  I  am  pleased  to  hear  from 
Dr.  Porter  that  an  effort  is  to  be  made  to  secure  a  state  law  along  similar 
lines. 

2.  Mr.  Choate,  in  his  opening  remarks,  touched  upon  the  importance  of 
early  diagnosis  of  tuberculosis.  An  important  aid  to  this  end,  which  is 
indeed  of  the  utmost  significance,  is  the  establishment  of  laboratories  main- 
tained by  municipal  and  state  boards  of  health  and  freely  at  the  service  of 
physicians. 

There  are  at  least  three  classes  of  institutions  which  are  of  primary 
importance. 

3.  First  in  importance  for  the  treatment  of  tuberculosis  are  sanatoria. 
This  country  owes  a  great  debt  to  Dr.  Trudeau,  the  pioneer  in  the  establish- 
ment of  sanatoria  for  tuberculosis  in  America  and  the  leader  in  the  crusade 
against  this  disease.  While  I  consider  that  hospitals  for  advanced  cases  of 
tuberculosis  are  more  important  than  sanatoria  in  the  prevention  of  the 
spread  of  tuberculosis,  still  the  latter  institutions  are  also  valuable  for  this 
purpose  in  accomplishing  the  arrest  of  the  disease  in  those  who  would  other- 
wise become  possible  sources  of  infection  and  especially  in  their  educational 
influence  extending  far  beyond  the  actual  inmates.  Here  the  great  lesson 
is  most  effectively  taught  that  by  proper  disposal  of  his  expectoration  and 
certain  simple  precautions  the  consumptive  may  render  himself  entirely 
harmless  as  a  source  of  infection  to  others. 

In  Germany  today  some  twenty-five  thousand  patients  in  the  early  stages 
of  tuberculosis  are  treated  in  sanatoria,  a  number  equal  to  about  one-fourth 
of  the  total  deaths  from  this  disease.  Sanatoria  on  such  a  scale  and  fre- 
quented by  patients  to  such  an  extent  must  rank  among  important  prevent- 
ive agencies. 


MEASURES  AGAINST  TUBERCULOSIS  635 

4.  Hospitals  for  the  isolation  of  advanced  cases  of  tuberculosis  are  given 
by  Koch  the  first  position  among  the  agencies  for  checking  the  spread  of  the 
disease,  and  their  importance  is  especially  emphasized  also  by  Dr.  Biggs. 
These  hospitals  unlike  the  sanatoria,  receive  the  patients  who  are  most 
dangerous  to  others  and  are  responsible  largely  for  the  spread  of  the  disease. 
Every  populous  community  should  be  provided  with  one  or  more  hospitals 
for  patients  in  the  advanced  stages  of  tuberculosis,  and  every  effort  should 
be  made  to  secure  the  transfer  to  the  hospital  of  such  patients,  when  they 
cannot  be  suitably  cared  for  in  their  homes.  Much  more  should  be  done  than 
is  now  customary  to  make  these  hospitals  attractive  to  these  patients  and 
their  friends.  One  of  the  greatest  difficulties  in  the  crusade  against  tuber- 
culosis at  the  present  time,  especially  in  this  country,  is  the  utterly  inade- 
quate provision  for  these  hospitals.  There  is  also  difficulty,  even  where  the 
hospitals  exist,  in  inducing  patients  to  enter  them  in  sufficient  numbers. 

Under  present  conditions  only  a  relatively  small  number,  in  this  country 
not  more  than  4  per  cent  at  best,  of  tuberculosis  patients  are  cared  for  either 
in  sanatoria  or  in  hospitals.  It  is  evident  that  through  some  other  agency 
the  largest  number  of  consumptives  must  be  reached.  This  is  now  being 
accomplished  more  and  more  effectively  and  in  constantly  increasing  measure 
by  the  special  tuberculosis  dispensary.  This  is  or  should  be  an  institution 
in  many  respects  different  from  what  is  ordinarily  understood  by  a  dis- 
pensary. The  German  conception  of  this  institution  is  expressed  by  the 
designation  "  information  and  aid  station."  The  French  idea  is  also  that 
of  an  antituberculosis  bureau,  forming  a  centre  for  the  enlightenment  of  the 
public,  for  hygienic  education,  for  the  discovery  of  centres  of  tuberculous 
infection  in  households  and  workshops,  for  the  instruction  of  patients  in  the 
precautions  necessary  to  prevent  spread  of  the  disease,  for  the  improvement 
of  living  and  working  conditions,  for  medical  care  and  kindred  purposes. 
Visiting  nurses  and  health  inspectors  constitute  an  essential  part  of  the 
machinery  of  these  tuberculosis  dispensaries,  which  we  must  rank  among  the 
most  important  and  effective  agencies  in  the  campaign. 

Time  forbids  more  than  the  mere  mention  of  such  recognized  preventive 
measures  as  the  disinfection  of  rooms  vacated  by  consumptives  through  death 
or  removal,  enforcement  of  laws  and  regulations  against  expectoration  in 
public  places,  protection  of  food,  especially  the  milk  supply,  by  suitable  laws 
and  their  enforcement,  sanitary  inspection  of  factories,  workshops,  lodging 
houses,  etc.,  destruction  of  tuberculous  sputum  and  the  education  of  con- 
sumptives, of  the  public  and  of  school  children  in  the  elementary  facts  re- 
garding the  origin  and  spread  of  tuberculosis,  and  in  ways  of  healthful 
living. 


636  MEASURES  AGAINST  TUBERCULOSIS 

Scarcely  less  important  than  measures,  like  the  foregoing,  specifically 
directed  against  tuberculosis,  are  all  conditions  which  make  for  the  improve- 
ment of  the  dwellings  and  working  places  of  the  poorer  classes.  Air,  light, 
and  food  are  as  important  for  the  prevention  as  for  the  cure  of  tuberculosis. 
Parks,  playgrounds,  in  a  word  all  measures  to  improve  the  health  of  the 
people,  operate  in  a  very  direct  way  in  increasing  resistance  to  tuberculosis 
and  in  lessening  chances  of  infection.  There  is  reason  to  believe  that  no 
small  part  in  the  diminution  of  the  amount  of  tuberculosis  has  been  due  to 
improvement  in  the  general  conditions  of  living. 

The  specific  measures  against  tuberculosis  must  be  carried  out  by  the  health 
officials  and  especial  emphasis  must  be  placed  upon  the  need  of  a  larger 
number  of  well  trained  sanitary  experts  in  the  work  of  our  state  and  munici- 
pal boards  of  health  and  of  larger  resources  at  their  disposal.  Upon  them 
must  fall  the  main  part  of  the  work  in  the  campaign  against  tuberculosis. 
With  some  notable  exceptions  our  city  and  state  boards  of  health  are  far 
behind  in  efficiency  similar  boards  in  England  and  Germany.  The  need  of 
special  training  for  the  successful  conduct  of  public  health  work  is  most 
inadequately  appreciated  by  the  general  public  and,  it  is  to  be  feared,  even 
by  the  medical  professions  in  this  country. 

Progress  in  the  struggle  against  tuberculosis  is  largely  a  question  of  ways 
and  means.  I  have  enumerated  some  of  the  more  important  agencies  needed 
for  the  control  of  this  disease  not  with  tlie  intention  of  outlining  a  pro- 
gramme, but  to  indicate  how  inadequately  at  present  preventive  measures 
are  in  operation  and  thereby  to  substantiate  the  opinion  tliat  wider  and  more 
effective  application  of  these  measures  would  yield  correspondingly  better 
results.  Much  larger  funds  are  needed  than  are  now  available,  but  it  can 
be  confidently  predicted  that  the  returns  in  the  saving  of  human  life  and  in 
increase  of  happiness  and  of  productiveness  will  be  out  of  all  proportion  to 
the  pecuniary  outlay. 

What  New  York  accomplishes  in  this  world-wide  movement  against  tuber- 
culosis and  the  way  she  accomplishes  it  liave  a  significance  not  limited  by 
tlie  boundaries  of  this  Empire  State.  An  especial  incentive  to  prompt  action 
is  the  opportunity  which  will  be  presented  next  September  of  demonstrating 
to  the  world  at  the  International  Congress  of  Tuberculosis  what  this  state 
has  done  and  is  doing  in  the  most  stupendous  struggle  against  disease  ever 
undertaken  bv  man. 


CONSIDEKATIONS  RELATING  TO  THE  CONTEOL  OF 
TUBEECULOSIS ' 

The  people  have  been  aroused  as  never  before  in  this  combat  against  the 
most  devastating  disease  of  mankind.  They  have  recognized  that  it  is  a 
disease  of  the  whole  people,  and  as  in  no  other  battle  the  question  arises, 
How  can  the  forces  which  have  been  aroused  be  directed  into  those  channels 
which  will  yield  the  best  results  in  the  shortest  time  and  the  most  economic 
way  ?  In  other  words,  what  course  of  action  should  be  taken  in  order  to 
secure  domination  of  this  terrible  disease?  All  these  various  agencies,  of 
which  the  campaign  is  composed,  must,  of  course,  be  brought  into  action, 
but  the  foundation  of  our  work  rests  upon  our  exact  knowledge  of  the  nature 
of  the  disease.  Our  exact  knowledge  of  the  mode  of  origin  and  spread  of  the 
disease  is  only  about  twenty-five  or  twenty-seven  years  old.  It  was  not  until 
the  fact  was  thoroughly  established  that  the  disease  was  due  to  a  micro- 
organism that  we  could  undertake  intelligent  measures  of  prevention.  We 
had  to  learn  much  more  as  to  the  nature  of  the  germ,  the  conditions  under 
which  the  disease  was  acquired  and  how  it  spread.  It  may  now  be  stated 
that  while  all  of  these  problems  have  not  yet  been  solved,  we  have  an  amount 
of  information  which  enables  us  to  state  positively  that  if  practical  measures 
based  upon  this  exact  scientific  knowledge  are  properly  applied,  the  amount 
of  tuberculosis  can  be  reduced  to  a  relatively  small  figure.  It  would  be  most 
hazardous  to  prophesy  how  soon  that  will  be,  but  it  is  safe  to  say  that  in  less 
than  one  generation  the  mortality  from  tuberculosis  will  be  cut  in  two  if 
we  apply  the  knowledge  we  already  possess. 

I  cannot,  of  course,  at  this  time  attempt  to  state  in  any  detail  what  should 
be  the  program  of  prevention,  but  it  may  not  be  out  of  place  to  run  over  a 
few  of  the  leading  measures  in  this  program.  As  a  consideration  of  first 
im})ortauce,  I  would  place  the  registration  of  all  cases  of  tuberculosis,  at 
least  in  tlie  larger  cities.  I  know  objections  have  been  raised  to  this,  and 
these  have  come  not  a  little  from  the  members  of  our  profession ;  but  in  reply 
to  those  objections  we  can  say  that  these  laws  have  already  been  applied  and 
successfully  carried  out  in  certain  cities.  That,  I  think,  is  a  sufficient  answer 
to  those  objections.    It  is  fundamental,  in  this  campaign,  that  there  should 

^  Report  of  an  address  delivered  before  the  National  Association  for  the  Study 
and  Prevention  of  Tuberculosis,  Washington,  D.  C,  May  14,  1909. 
Nat.  Ass.  Study  &  Prev.  Tuberc,  Tr.,  Phila.,  1909,  V,  34-36. 

637 


638  CONTROL  OF  TUBERCULOSIS 

be  notification  and  registration.  We  should  know  of  the  existence  of  the 
disease;  where  it  is  and  how  much  there  is  of  it.  There  should  be  everywhere 
also  means  at  the  disposal  of  the  physician  for  the  prompt  and  accurate  diag- 
nosis of  the  disease,  because  the  sooner  it  is  recognized,  the  better  the  results, 
in  both  prevention  and  treatment.  We  now  come  to  institutional  treatment, 
of  whicli  there  should  be  a  number  of  types,  and  each  of  these  has  its  part  to 
play  in  this  preventive  campaign.  The  first  of  these  in  importance  is  tlie 
sanatorium  for  the  treatment  of  the  early  cases.  One  of  the  greatest  blessings 
to  mankind  has  been  the  establishment  of  these  sanatoria,  where  patients 
with  tuberculosis  in  its  earlier  stages  can  be  cured.  There  is  no  agency  which 
makes  so  strong  an  humanitarian  appeal  as  the  sanatorium,  and  it  takes  tlie 
very  first  place  in  the  preventive  campaign  against  tuberculosis. 

Another  kind  of  institution  is  the  hospital  for  advanced  cases,  and  this 
leads  me  to  the  central  point  of  what  I  have  to  say.  In  Scotland  and  Ireland, 
as  well  as  in  England  and  Wales,  and  especially  in  Germany,  there  has  been 
a  notable  reduction  in  the  death  rate  from  tuberculosis.  Now,  of  course, 
it  must  be  evident  to  you  that  if  we  can  put  our  finger  upon  precisely  the 
factor  or  factors  which  are  responsible  for  this  reduction  in  the  mortality 
of  tuberculosis,  we  have  there  tlie  agency  or  agencies  which  we  should  bring 
into  operation  immediately.  It  is  not  so  easy  to  say  exactly  what  has  been 
responsible  for  this  progressive  diminution  in  the  amount  of  tuberculosis, 
and  it  would  lead  altogether  too  far  if  I  should  attempt  to  bring  before  you 
the  various  opinions  on  this  subject,  but  I  would  like  to  state  what  is  the 
conclusion  of  the  highest  authorities  on  this  subject,  men  who  have  studied 
this  matter  very  fully,  such  as  Koch  in  Germany,  and  Arthur  Xewsholme, 
the  best  vital  statistician  in  English-ispeaking  countries.  Botli  of  these 
authorities  are  of  the  opinion  that  the  factor  that  has  done  the  most  is  what 
is  called  institutional  segregation.  That  means  the  isolation  of  patients 
with  tuberculosis  so  far  as  is  possible,  in  institutions.  That  should  be 
emphasized  today  as  the  central  feature  of  the  campaign  against  tul^erculosis, 
and  the  great  need  in  this  country  is  a  supply  of  suitable  hospitals  for  these 
cases  of  advanced  tuberculosis.  That  does  not  make  the  same  appeal  as  does 
the  establishment  of  sanatoria.  You  have  two  patients,  one  hopelessly  ill, 
the  other  a  young  man  in  the  early  stages  of  the  disease.  It  is  the  latter  that 
makes  the  strongest  humanitarian  appeal.  Hence,  we  can  leave  to  a  much 
larger  extent  the  establishment  of  these  sanatoria  to  private  philanthropy, 
wiiile  it  is  to  the  legislature  and  public  health  boards  that  we  must  look  for 
the  segregation  of  tlie  more  advanced  cases.  By  that  we  will  doubtless  gain 
more  than  by  any  other  single  factor.  Further  than  this,  I  believe  the  time 
has  come  when  we  should  emphasize  the  importance  of  institutional  segrega- 
tion as  the  most  important  factor  in  reducing  the  incidence  of  the  disease; 


CONTROL  OF  TUBERCULOSIS  639 

and  in  dealing  with  patients  who  are  a  serious  menace  to  the  community 
and  who  cannot  or  will  not  be  taught  to  take  proper  safeguards  against  the 
infection  of  their  fellow-men,  I  think  that  the  health  authorities  should  be 
empowered  to  place  them  in  proper  institutions. 

Another  agency  that  should  be  considered  in  this  connection  is  the  dis- 
pensary for  tuberculosis.  It  is  there  that  many  of  these  patients  first  apply 
for  treatment,  and  it  is  there  that  the  plans  of  this  campaign  are  more  or 
less  centralized.  However,  I  cannot  elaborate  further  on  these  points. 
These  institutions,  their  establishment  and  maintenance,  cost  money,  but 
the  amount  of  money  which  is  expended,  in  proportion  to  the  return,  is  most 
trifling.  The  returns  to  the  community  are  out  of  all  proportion  to  the  sum 
required.  It  has  been  estimated  that  it  would  increase  by  only  about  50 
per  cent  the  cost  of  the  dependent  poor  already  provided  for  by  the  state. 
Fewer  would  have  to  be  provided  for  than  are  provided  for  now  in  the  insane 
hospitals.  When  you  estimate  how  prevalent  tuberculosis  is  today,  and 
how  great  a  loss  it  entails  upon  the  community,  who  could  hesitate  to  go 
before  our  legislatures,  with  this  great  force  of  public  sentiment  behind  us, 
and  demand  that  they  shall  carry  out  a  program  which  rests  upon  exact 
knowledge,  and  which  will  yield  returns  beyond  all  conception  as  to  their 
final  value  to  mankind. 

The  proper  housing  of  the  poor  and  the  establishment  of  playgrounds  are 
incidental  to  the  problem  under  discussion,  but  do  not  represent  the  central 
idea.  The  prophylaxis  of  tuberculosis  makes  such  a  strong  appeal  to  the 
community  because  everything  connected  with  it  leads  to  better  conditions ; 
but  all  diseases  are  similar  in  that  respect.  The  same  holds  true  in  regard 
to  the  prevention  of  typhoid  fever  and  malaria.  All  these  factors  are  of 
importance,  and  we  can  use  everyone  to  the  greatest  advantage,  but  never- 
theless we  should  make  it  clear  to  the  public  that  there  are  a  few  definite 
agencies  which  should  first  be  emphasized  as  the  central  ideas  of  our  program, 
and  which  give  the  greatest  promise  of  return. 


THE  SIGNIFICANCE  OP  THE  GREAT  FREQUENCY  OF  TUBER- 
CULOUS INFECTION  IN  EARLY  LIFE  FOR  PRE- 
VENTION OF  THE  DISEASE' 

Permit  me,  in  behalf  of  the  members  of  the  Association,  to  extend  a  wel- 
come to  all  our  guests ;  also  to  express  our  gratification  at  this  opportunity 
of  meeting  in  the  city  of  Denver.  The  custom  of  the  Association  as  a  national 
organization  has  been  to  meet  in  the  city  of  Washington.  There  has  been 
only  one  exception  to  this  rule  in  the  past,  namely  the  meeting  held  in  1908 
in  the  city  of  Chicago,  for  which  there  were  special  reasons.  This  meeting, 
therefore,  marks  a  departure  from  our  precedents,  but  one,  which,  I  think  is 
to  be  welcomed.  I  believe  the  influence  of  the  Association  will  be  extended 
by  meeting  occasionally,  say  once  in  three  or  four  years,  outside  of  the  city 
of  Washington.  While  it  is  important  to  preserve  the  national  character  of 
the  Association,  it  is  likewise  important  to  extend  the  influence  of  the  Asso- 
ciation and  its  benefits  by  occasional  meetings  in  different  parts  of  the 
country. 

With  peculiar  satisfaction  I  express  our  pleasure  in  meeting  in  this  city, 
which  has  been  so  actively  identified  with  the  anti-tuberculosis  movement. 
We  shall  certainly  feel  well  repaid  if  this  meeting  is  a  help  in  any  way  to 
the  great  cause  in  which  we  are  engaged,  and  I  am  confident  that  the  Asso- 
ciation itself  will  derive  great  advantage  from  meeting  in  this  place.  We 
have  experienced  already  enough  of  hospitality  and  of  the  excellent  arrange- 
ments for  our  meeting  to  justify  me  in  expressing  even  now  our  thanks  to 
the  committee  of  arrangements  and  to  all  who  have  cooperated  with  them. 

Since  our  last  meeting,  my  predecessor  in  this  office.  Dr.  Edward  G. 
Janeway,  has  passed  away,  and  it  is  fitting  that  we  should  pay  our  tribute  to 
the  memory  of  this  great  physician,  who  enjoyed  to  an  unusual  degree  the 
confidence  and  esteem  of  all  his  colleagues,  and  was  one  of  the  most  influ- 
ential and  useful  men  who  have  adorned  the  profession  of  medicine  in 
America.  His  remarkable  powers  as  a  diagnostician,  which  to  some  seemed 
almost  intuitive,  rested  ujjon  long  years  of  training,  the  first  fifteen  years  of 
his  professional  life  being  devoted  largely  to  that  combination  of  work  in  the 

'  President's  address  delivered  before  the  Seventh  Annual  Meeting  of  the 
National  Association  for  the  Study  and  Prevention  of  Tuberculosis,  Denver,  Col., 
June  20,  1911. 

Nat.  Ass.  Study  &  Prev.  Tuberc,  Tr.,  Phila.,  1911,  VII,  17-28. 
640 


FREQUENT  TUBERCULOSIS  IN  EARLY  LIFE     641 

deadhouse  with  close  observation  in  the  hospital  wards  which  has  been  the 
basis  of  the  diagnostic  skill  of  so  many  famous  physicians. 

Dr.  Janeway  was  interested  greatly  in  the  subject  of  tuberculosis  and  in 
the  movement  to  which  we  are  committed.  Dr.  Knopf  has  kindly  furnished 
me  with  data  which  I  hope  he  will  embody  in  an  article  pointing  out  many 
of  the  specific  contributions  of  Dr.  Janeway  to  the  subject  of  tuberculosis. 
He  and  Dr.  Austin  Flint,  the  elder,  were  among  the  first  in  this  country  to 
recognize  the  significance  of  Koch's  discovery  in  1882  of  the  tubercle  bacillus. 
Even  shortly  before  that  he  published  a  paper  on  the  contagiousness  of  pul- 
monary tuberculosis.  It  is  rather  difficult  to  trace  all  the  contributions  of 
Dr.  Janeway  through  his  published  writings.  For  this  purpose  it  is  neces- 
sary to  go  through  the  reports  of  societies,  and  especially  the  discussions  in 
societies.  He  made  a  large  number  of  reports  to  the  New  York  Pathological 
Society.  Without  exhaustive  search  I  have  counted  not  less  than  seventy 
published  contributions  of  Dr.  Janeway,  a  record  which,  while  not  prolific, 
is  certainly  not  sterile,  when  one  considers  the  value  of  his  papers. 

Tlie  great  work  of  the  New  York  City  Board  of  Health  in  initiating  the 
municipal  control  of  tuberculosis,  with  which  a  former  president  of  the  Asso- 
ciation, Dr.  Hermann  Biggs,  has  been  so  actively  identified,  received  from 
the  beginning  the  active  and  influential  support  and  advice  of  Dr.  Janeway. 
He  was  prominent  in  the  work  of  the  Committee  on  Prevention  of  Tubercu- 
losis of  the  Charity  Organization  Society  of  the  City  of  New  York,  and  of  that 
of  the  New  York  State  Charities  Aid  Association.  He  was  much  sought  for 
as  a  member  of  committees,  for  the  voice  of  no  medical  man  carried  greater 
weight  with  the  public. 

I  shall  ask  the  audience  to  rise  in  respect  to  the  memory  of  Dr.  Janeway. 

Shortly  after  our  meeting  last  year,  early  in  May,  there  died  Robert  Koch, 
to  whose  great  discoveries  is  due  the  movement  against  tuberculosis  which 
was  the  occasion  for  the  organization  of  this  Association  and  to  which  our 
presence  here  today  is  due. 

The  name  of  Robert  Koch  is  immortal  in  the  history  of  medicine.  He  was 
endowed  with  the  divine  genius  for  scientific  discovery,  and  was  undoubtedly 
one  of  the  greatest  benefactors  of  his  kind  who  has  ever  lived.  We  have  only 
begun  to  reap  the  benefits  to  be  derived  from  his  discoveries.  Generation 
after  generation  will  continue  to  glean  the  harvest. 

The  real  significance  of  Koch's  work  is  that  he  gave  us  the  key  which 
enables  us  to  unlock  the  secrets  of  that  class  of  diseases,  the  infectious,  which 
are  of  the  greatest  racial  and  social  significance  to  mankind,  whereby  medi- 
cine, and  especially  preventive  medicine  has  been  revolutionized.  ]\Iedicine 
has  come  into  relation  with  the  problems  of  society  in  a  way  never  before 


642  FREQUEXT  TUBERCULOSIS  IX  EARLY  LIFE 

approached,  and  has  a  part  to  play  of  the  highest  significance  for  human 
welfare. 

The  greatest  of  Koch's  discoveries  is  that  of  the  tubercle  bacillus,  an- 
nounced in  1882,  not  quite  three  decades  ago.  Not  even  Koch  himself,  far 
less  others,  could  foresee  all  the  beneficial  results  which  would  flow  from  this 
discovery,  nor  can  we  realize  it  all  today. 

Koch's  interest  in  the  subject  of  tuberculosis  was  paramount.  He  not 
only  introduced  the  methods  which  enable  us  to  learn  the  mode  of  origin  and 
spread  of  this  disease,  but  he  continued,  for  over  thirty  years,  a  leader  in 
investigation  in  this  field.  It  is  rare  that  man  opens  the  path  and  at  the 
same  time  enters  in  and  reaps  such  a  rich  harvest  as  Koch  did. 

Koch's  discovery  and  study  of  tuberculin,  while  at  first  arousing  hopes 
destined  to  disappointment,  have  proved  to  be  of  vast  significance,  not  merely 
in  their  practical  bearings,  but  in  elucidating  many  problems  connected  with 
tuberculosis  and  other  infections.  I  need  in  this  connection  only  to  remind 
you  of  the  interest  which  now  attaches  to  the  subject  of  hypersusceptibility 
or  anaphylaxis  of  which  the  tuberculin  reaction  is  an  example. 

Koch's  pronouncement  on  the  question  of  the  relation  of  human  to  bovine 
tuberculosis,  bitterly  contested  as  it  has  been,  has  been  of  great  service  in 
advancing  our  knowledge  of  a  subject  of  great  practical  as  well  as  scientific 
importance.  It  may  be  doubted  whether  a  voice  less  pow'erful  than  his  could 
have  arrested  the  attention  of  investigators  and  have  led  to  such  numerous 
and  valuable  investigations  as  those  which  are  now  bringing  the  opinions  of 
scientific  students  into  fair  agreement  as  to  the  extent  and  character  of  the 
dangers  to  human  l)eings  from  bovine  tuberculosis. 

We  recall  with  especial  gratification  Professor  Koch's  visit  to  this  country 
and  his  participation  in  the  International  Congress  on  Tuberculosis  in 
Wasliington  in  1908,  to  which  he  gave  such  luster. 

I  would  like  to  add  a  word  about  another  important  contributor  to  our 
knowledge  of  tuberculosis  who  has  passed  away  more  recently,  namely,  Pro- 
fessor Arloing,  of  Lyons,  France.  I  speak  of  him  particularly  on  account  of 
the  charming  impression  which  he  made  upon  all  who  met  and  heard  him  at 
the  International  Congress  on  Tuberculosis  in  Washington.  He  was  one  of 
that  agreeable  and  important  group  of  French  colleagues  who  honored  us  by 
their  presence,  and  I  feel  that  you  would  wish  me  to  pay  at  least  this  tribute 
of  a  few  words  to  the  memory  of  one  for  whom  we  came  to  have  great  admi- 
ration, almost,  I  may  say,  affection,  on  account  of  his  delightful  personality. 
He  is  a  real  loss  to  the  cause  of  tuberculosis,  and  especially  to  that  in  France. 
It  is  significant  that  in  the  city  of  Lyons,  where  he  worked,  in  contrast  with 
BO  many  of  the  French  cities,  there  has  been  a  decided  decline  in  tlie  inci- 
dence and  niortaiity  from  tuberculosis. 


FOU  PREVENTION  OF  THE  DISEASE  643 

The  Association  has  reason  to  feel  much  gratification  at  the  work  which 
it  has  done  in  the  six  years  since  it  was  started.  While  the  general  aims  of 
the  Association  have  been  clear  from  the  first,  there  has  been  no  attempt  to 
formulate  a  definite  program.  The  effort  has  been  to  further  the  propaganda 
against  tuberculosis  in  a  national  way,  and  to  direct  our  energies  in  channels, 
which,  for  the  time  being,  seemed  most  promising,  so  far  as  the  resources  of 
the  Association  permitted.  The  effort  has  been  to  stir  up  general  interest  in 
the  subject,  and  especially  to  aid  and  encourage  local  organized  movements. 
When  we  consider  the  large  number  of  associations  against  tuberculosis 
which  have  started  during  these  years,  numbering  now,  I  believe,  nearly  five 
hundred,  many  in  affiliation  with  our  national  body,  and  initiated  through  its 
efforts;  when  we  regard  the  good  that  has  been  done  by  our  traveling  exhibits, 
going  from  place  to  place,  accompanied  with  lecturers,  and  usually  associated 
with  public  meetings  stimulating  the  interest  of  physicians  and  the  general 
public  wherever  they  go;  when  we  note  the  specific  contributions  in  the 
Transactions  of  the  Association,  and  the  stimulating  infiuences  of  our  meet- 
ings, it  is  e\'ident  that  the  relatively  small  amount  of  money  which  we  have 
had  at  our  disposal  has  accomplished  an  immense  amount  of  good.  We  have 
received  generous  contributions  from  individuals,  and  we  have  reason  to  be 
especially  grateful  to  the  Eussell  Sage  Foundation,  without  whose  generous 
aid  our  work  would  have  been  seriously  curtailed. 

We  can  look  forward  most  hopefully  to  the  continued  and  enlarged  activi- 
ties of  this  Association.  You  will  all  wish  me,  I  am  sure,  in  this  connection 
to  express  our  appreciation  and  thanks  to  our  very  energetic  and  able  execu- 
tive secretary.  Dr.  Farrand,  who  is  really  the  one  so  largely  responsible  for 
it  all,  working  with  singular  unselfishness,  devotion,  intelligence,  and  sym- 
pathy in  this  great  cause. 

There  are  so  many  topics  which  I  should  like  to  bring  before  the  Associa- 
tion that  I  am  somewhat  embarrassed  at  attempting  a  selection.  I  should 
like  to  say  a  word,  at  least,  with  reference  to  the  scientific  basis  of  the  cam- 
paign against  tuberculosis.  It  is,  of  course,  self-evident  that  rational  and 
effective  measures  of  prevention  against  any  infectious  disease  must  be  based 
upon  as  exact  knowledge  as  possible  concerning  the  modes  of  origin  and  of 
propagation  of  that  disease,  and  it  is  because  we  have  at  least  a  measure  and 
a  saving  measure  of  such  knowledge  relating  to  tuberculosis  that  we  are 
engaged  in  the  campaign,  which  is  so  full  of  hope,  but  no  one  would  pretend 
that  there  are  not  before  us  many  unsolved  problems.  No  one  would  claim 
that  our  preventive  measures  could  not  be  more  effective,  more  economically 
concentrated,  more  intelligently  directed  if  a  good  many  of  these  problems 
were  solved.    Did  we  know  more  precisely,  for  instance,  the  paths  of  infec- 


644  FEEQUENT  TUBERCULOSIS  IN  EARLY  LIFE 

tion  ;  did  Ave  know  the  full  significance  of  the  almost  universal  infection  with 
tubercle  bacilli,  at  least  in  certain  strata  of  the  commmiity,  in  the  early 
years  of  life  did  we  know,  in  a  word,  a  great  deal  more  concerning  the  origin 
and  spread  and  nature  of  the  disease,  we  would  certainly  be  better  armed  to 
fight  this  enemy.  We  should,  therefore,  always  in  this  Association  keep  in 
mind  the  importance  of  having  the  scientific  side  represented,  as  is  now  done 
in  our  pathological  and  clinical  sections,  and  our  sociological  brethren, 
whom  we  are  glad  to  have  with  us,  must  bear  with  us  at  times  in  the  presenta- 
tion of  subjects  of  somewhat  special  and  technical  interest,  which  they  may 
not  feel  bear  directly  and  immediately  upon  the  campaign.  On  the  other 
hand,  the  scientific  members  must  welcome  all  the  aid  which  those  engaged  in 
great  social  reforms  can  render.  It  is  here  in  this  Association,  as  it  is  in  the 
whole  movement,  that  all  the  forces  of  society  must  be  coordinated,  and  the 
Association  is  fortunate  in  having  secured  the  cohesion  of  all  who  are  inter- 
interested  in  the  subject  of  tuberculosis,  whatever  may  be  the  special  line  of 
interest  and  activity. 

The  important  subject  of  the  portals  of  entry  and  paths  of  infection  for 
the  tubercle  bacillus  is  to  be  treated  by  Dr.  Ophiils,  the  chairman  of  the 
Pathological  Section. 

I  have  referred  to  the  work  which  has  been  done  to  determine  the  share  of 
tubercle  bacilli  of  bovine  origin  in  causing  human  tuberculosis.  There  is 
now  general  agreement  of  opinion  that  bovine  bacilli  are  negligible  as  a 
cause  of  pulmonary  consumption,  the  only  question  left  open  being  the 
possibility  of  the  transformation  of  the  bovine  into  the  human  type  by  pro- 
longed survival  in  the  human  host,  a  view  for  which,  at  present,  there  is 
ver}'  little  satisfactory  evidence.  When  one  considers  that  most  of  the 
cases  of  open  tuberculosis,  which  are  the  chief  source  of  danger  in  spread- 
ing the  disease,  are  pulmonary  infections,  it  is  apparent  that  a  good  share 
of  Koch's  contention  upon  this  suliject  has  been  substantiated. 

There  is  no  doubt,  however,  that  Koch  gave  a  somewhat  misleading  im- 
pression, and  underestimated  the  risks  of  infection  from  bovine  sources. 
Such  infection  plays  a  role  by  no  means  negligible  in  the  tuberculosis  of 
infancy  and  childhood,  particularly  in  the  scrofulous  infections  of  lymphatic 
glands  and  of  other  parts,  which  are  so  common  at  that  period  of  life.  Our 
prophylactic  measures,  therefore,  should  not  neglect  the  dangers  of  tubercu- 
losis infection  from  milk,  although  those  dangers  are  far  exceeded  by  the 
risks  from  human  sources. 

The  most  important  contributions  which  have  been  made  in  recent  years  to 
the  genesis  and  pathology  of  tul)crculosis  are  those  concerned  with  the  study 
of  tuberculosis  infection  in  infancy  and  childhood,  and  tlie  interpretation  of 


FOR  PREVENTION  OF  THE  DISEASE  645 

the  bearings  of  such  infection  upon  the  manifestations  of  the  disease,  partic- 
ularly upon  pulmonary  consumption,  in  later  life.  I  wish  more  particularly 
to  call  your  attention  to  some  of  the  results  of  these  investigations. 

The  first  thorough  investigation  of  the  frequency  of  tuberculosis  infection 
in  human  beings  was  made  by  Nageli  and  published  in  1900,  He  found 
that  97  per  cent  of  adults  examined  at  autopsy  in  Ziirich  showed  either 
active  latent,  or  healed  tuberculosis ;  in  other  words,  that  infection  with  the 
tubercle  bacillus  is  practically  universal  by  the  time  adult  life  is  reached. 
That  is,  of  course,  not  equivalent  to  saying  that  every  one  has  or  has  had  the 
disease,  tuberculosis.  It  signifies  merely  that  in  the  class  examined  prac- 
tically every  one  had  received  into  the  body  tubercle  bacilli,  and  that  these 
had  left  their  record  behind.  NageU's  observations  startling  as  they  seem, 
have  been  confirmed  by  similar  methods  elsewhere,  notably  by  Burckhardt  in 
Dresden. 

Further  studies  have  shown  that  in  the  great  majority  of  cases  this  almost 
universal  infection  with  tubercle  bacilli  in  the  classes  examined  dates  from 
before  the  fourteenth  year  of  age.  This  conclusion  is  based  partly  upon 
autopsies,  especially  of  those  tested  during  life  with  tuberculin,  and  partly 
upon  the  results  of  the  testing  of  large  numbers  of  infants  and  children  for 
the  tuberculin  reaction  by  the  harmless  cutaneous  and  puncture  methods. 
There  is  every  reason  to  believe  that  a  positive  result  of  these  delicate  tests 
is  certain  evidence  of  an  existing  or  healed  tuberculous  infection. 

By  means  of  data  of  this  character  it  has  been  demonstrated  by  Hamburger 
and  Monti  that  about  95  per  cent  of  all  the  children  in  the  Vienna  hospitals 
are  already  tuberculous  by  the  time  they  reach  the  twelfth  to  the  thirteenth 
year  of  life.  Similar  results  have  been  obtained  in  Prague,  and  it  is  probable 
that  they  hold  true  for  children  of  the  poorer  classes  in  other  large  cities. 
While  the  percentage  is  doubtless  considerably  smaller  for  children  of  the 
well-to-do  and  in  smaller  towns  and  country  places,  the  significance  of  the 
figures  cited  is  scarcely  diminished  thereby,  for  it  is  especially  to  the  poorer 
classes  that  our  measures  of  prevention  in  the  control  of  tuberculosis  as  a 
racial  problem  must  be  directed. 

In  considering  this  question  of  the  frequency  of  tuberculosis  we  must,  as 
already  mentioned,  keep  clear  in  our  minds  the  distinction  between  tubercu- 
losis as  a  cause  of  death  and  tuberculosis  as  found,  often  only  after  long 
and  patient  search,  as  an  accessory  lesion  in  the  inactive,  latent,  or  healed 
forms.  Regarded  from  this  point  of  view,  it  is  important  to  note  that  in 
the  first  weeks  of  life  tuberculosis  in  any  form  and  the  positive  tuberculin 
reaction  are  extremely  uncommon.  During  the  second  half  of  the  first  year 
of  life  the  number  of  cases  increases,  and  in  the  second  year  tliey  are  no 
longer  uncommon,  and  when  the  infection  is  found  at  this  period,  it  is 


646  FREQUENT  TUBERCULOSIS  IN  EARLY  LIFE 

usually  as  the  cause  of  death,  most  frequently  as  a  tuberculous  meningitis 
or  acute  miliary  tuberculosis.  After  this  period,  up  to  the  age  of  puberty, 
while  the  percentage  of  cases  increases  year  by  year,  reaching  over  90  per 
cent  by  this  time,  the  infection  appears  more  and  more  frequently  as  an 
inactive  or  healed  lesion,  fatal  tuberculosis  being  relatively  uncommon. 

As  has  long  been  known,  pulmonary  consumption  is  rare  in  the  first 
decade  and  a  lialf  of  life,  the  prevailing  forms  of  tuberculosis  in  the  earlier 
years  being  tuberculous  meningitis  and  acute  miliary  tuberculosis,  and  after 
the  third  or  fourth  years  chronic  lymphatic  disease  and  affections  of  the  bones 
and  joints.  It  is  not,  however,  justifiable  to  infer  from  the  prevalence  of 
these  types  that  the  primary  infection  has  been  through  the  alimentary 
canal,  as  in  the  vast  majority  of  cases  of  tuberculosis  in  infancy  and  child- 
hood there  exists  tuberculosis  of  the  bronchial  lymphnodes,  usually  associated 
with  a  focus  in  the  lungs. 

In  the  light  of  these  facts  we  must  concede  that  von  Behring  was  right  in 
his  statement  that  in  the  great  majority  of  instances  pulmonary  consump- 
tion develops  in  an  individual  who  has  previously  been  infected  with  the 
tubercle  bacillus,  although  he  was  in  error  in  his  view  that  the  primary 
infection  usually  dates  from  the  first  year  of  life  and  is  derived  from  the 
milk  of  tuberculous  cows. 

Much  light  has  been  thrown  upon  the  significance  of  this  startling  fre- 
quency of  primary  tuberculous  infection  in  early  life,  as  regards  its  bearing 
upon  the  genesis  of  pulmonary  phthisis,  by  the  study  of  the  influence  of 
an  existing  tuberculosis  upon  renewed  infection  with  the  tubercle  bacilli. 

Koch,  in  his  first  study  of  tuberculin,  observed  that  a  tuberculous  guinea 
pig  behaves  differently  from  a  normal  one  when  reinfected  with  tubercle 
bacilli.  In  the  former  the  reaction  is  immediate  and  is  followed  by  a  local 
necrosis,  ending  in  complete  healing  of  the  site  of  reinfection,  unless  the  dose 
of  bacilli  be  too  large.  This  observation  comparatively  neglected  by  subse- 
quent experimenters,  has  been  made  the  starting  point  in  the  last  few  years 
of  interesting  experimental  studies  by  Romer  and  Joseph,  Hamburger,  and 
others.  That  a  measure  of  protection  may  be  afforded  by  previous  inocula- 
tions with  tubercle  bacilli  was  demonstrated  experimentally  by  Trudeau  in 
1890. 

On  account  of  the  high  degree  of  susceptibility  of  guinea  pigs  it  requires 
special  methods  of  inoculation  and  small  doses  of  tubercle  bacilli  to  demon- 
strate readily  the  protective  influence  of  an  existing  tuberculous  infection  of 
limited  extent  to  reinfection,  but  such  demonstration  has  been  conclusively 
brought  by  Romer  and  by  Hamburger.  Particularly  impressive  and  con- 
vincing are  Romer's  experiments  with  the  tuberculous  reinfection  of  sheep, 
which  closely  resemble  man    in   their   sensitiveness  to  tuberculin.     These 


FOR  PREVENTION  OF  THE  DISEASE  647 

animals  may  be  rendered  by  a  localized  tuberculosis  completely  insusceptible 
to  the  subsequent  intravenous  injection  of  quantities  of  bacilli  which  kill  the 
control  animals  in  a  few  weeks  with  generalized  tuberculosis. 

The  condition  which  is  present  in  these  animals  as  the  result  of  a  localized 
tuberculous  infection  is  that  designated  by  von  Pirquet  as  allergy,  and  is 
characterized  at  once  by  immunity  and  by  hypersusceptibility,  the  former 
being  manifest  upon  the  introduction  of  small  or  moderate  doses  of  tubercle 
bacilli,  which  are  readily  disposed  of,  and  the  latter  by  the  death  of  the 
animal  or  rapid  development  of  the  disease  when  the  doses  are  excessive.  In 
both  instances  the  reaction  follows  speedily  the  reinfection. 

There  would  appear  to  be  also  significant  differences  in  the  character  of 
the  tuberculous  lesions  according  as  these  are  the  result  of  a  primary  in- 
fection or  of  a  reinfection.  It  has  long  been  known  that  ulcerative  pulmo- 
nary tuberculosis  is  rarely  produced  experimentally  in  animals,  and  the 
usual  assumption  has  been  that  they  are  but  little  susceptible  to  this  form 
of  tuberculosis,  so  common  in  human  beings,  but  this  cannot  be  the  com- 
plete explanation.  In  1894  Prudden  demonstrated  to  the  Association  of 
American  Physicians  genuine  pulmonary  phthisis  in  tuberculous  rabbits 
subjected  to  secondary  intratracheal  streptococcus  inoculations.  Concur- 
rent or  mixed  infections,  however,  are  not  necessary,  as  it  has  been  shown 
by  von  Behring  and  others  that  phthisis  can  be  induced  by  renewed  inocula- 
tions with  tubercle  bacilli  in  animals  already  tuberculous.  Reinfections  from 
without  are  not  absolutely  necessary,  provided  there  exist  the  proper  ratio 
between  the  degree  of  resistance  of  the  animal  and  the  number  and  virulence 
of  the  bacilli.  Given  this  condition,  a  single  inoculation,  even  in  guinea 
pigs,  has  been  known  to  produce  a  progressive  chronic  tuberculosis,  resem- 
bling phthisis  in  man,  but  here  it  may  well  be  that  there  are  repeated  auto- 
inoculations,  such  as  are  assumed  to  occur  in  man  in  chronic  progressive 
tuberculosis. 

There  is  abundant  evidence  tliat  human  beings,  as  well  as  animals,  are 
protected  by  slight  or  limited  tuberculous  infections,  dating  in  the  former, 
as  has  been  stated,  usually  from  childhood,  against  the  effects  of  renewed 
inoculation  with  tubercle  bacilli  both  from  without  the  body  and  from 
within.  It  is  by  virtue  of  the  alteration  or  allergy  effected  by  the  primary 
tuberculous  infection  that  the  subsequent  entrance  of  tubercle  bacilli  from 
without  or  their  distribution  from  the  primary  focus  to  other  parts  of  the 
body  leaves  no  record  behind  in  the  majority  of  cases,  for  it  is  impossible  to 
suppose  that  the  two  or  three  old  scars  or  foci  of  tuberculous  infection  usually 
found  represent  the  only  penetrations  of  bacilli  into  the  body  during  the  life 
time  of  the  individual. 

Gratifying  as  is  the  recognition  of  tlie  protective  value  of  an  existing  tuber- 
culous focus  of  limited  extent,  we  must  keep  in  view  that  there  is  another 


648  FREQUEXT  TUBERCULOSIS  IN  EARLY  LIFE 

side  to  the  shield,  and  that  it  is  precisely  upon  the  basis  of  the  altered  reac- 
tion resulting  from  a  primary  infection  that  pulmonary  consumption  de- 
velops. Here  there  are  doubtless  many  factors  concerned  which  require 
further  clinical,  anatomical,  and  experimental  study  before  we  shall  reach 
a  satisfactory  understanding  of  the  pathogenesis  of  pulmonary  phthisis. 

We  are  in  the  dark  as  to  the  relative  frequency  in  the  causation  of  pulmo- 
nary consumption  of  auto-inoculations  from  existing  tuberculous  foci  or  of 
reinfections  from  without,  but  in  view  of  the  difficulty  of  tracing  sources  of 
infection  in  individual  cases  it  is  important  to  learn  that  it  is  not  necessary 
to  have  recourse  to  extraneous  infections,  and  my  own  belief  is  that  in  many 
instances  pulmonary  consumption  results  from  auto-inoculations  from  pre- 
viously inactive  or  latent  foci  of  tuberculosis  in  the  lungs  or  bronchial  glands, 
possibly  in  other  parts  of  the  body. 

Furthermore,  we  lack  precise  information  concerning  the  causes  which 
determine  the  occurrence  of  pulmonary  consumption  as  the  result  of  rein- 
fections. It  is  probable  that  in  some  instances  the  explanation  is  to  be 
found  in  the  massive  doses  of  bacilli  received  into  the  lungs,  or  in  their 
repeated  introduction  at  shore  intervals  of  time,  but  it  seems  difficult  for 
many  cases  to  dispense  with  the  doctrine  that  the  resistance  of  the  individual 
is  lowered  as  the  result  of  unfavorable  conditions  of  health  and  of  living. 
There  still  remains  room  for  appealing  to  the  various  factors  which  have  so 
often  been  presented  as  influencing  the  disposition  of  the  individual  to 
tuberculosis. 

Another  question  requiring  investigation  is,  Whether  immunity  persists 
after  complete  disappearance  of  all  tubercle  bacilli  from  the  body,  and  if  so, 
how  long?  In  view  of  the  difficulty  of  making  sure  that  there  are  no  living 
bacilli  in  the  body,  the  question  is  not  easy  to  settle,  but  the  evidence  iseems 
to  be  in  favor  of  a  return  of  susceptibility  within  a  certain  period  after  com- 
plete recovery. 

Although  analogies  in  medicine  are  dangerous,  there  is  much  which  is 
suggestive  in  that  which  has  often  been  drawn  in  recent  years  between  tuber- 
culosis and  syphilis.  In  both  diseases  an  existing  infection  affords  protection 
from  reinfections,  and  both  are  characterized  by  a  remarkable  "  Umstim- 
mung  "  of  the  system  of  allergy,  whereby  primary  infections  pursue  a  course 
different  from  the  later  manifestations  of  the  disease,  which  in  both  affec- 
tions are  marked  by  extensive  caseous  masses,  with  a  greater  tendency  to 
liquefy  and  form  cavities  in  tuberculosis  than  in  syphilis.  According  to  this 
analogy,  pulmonary  consum))tion  would  correspond  to  the  late  or  tertiary 
lesions  of  syphilis.  I  do  not  think,  however,  that  we  are  justified  in  pressing 
this  analogy  too  far. 

It  hardly  needs  to  be  emphasized  that  the  facts  which  I  have  briefly 
sketched  have  important  bearings  upon  methods  of  prevention  of  tubercu- 


FOR  PREVENTION  OF  THE  DISEASFi  649 

losis,  and  must  be  taken  into  consideration  in  formulating  the  plan  of  cam- 
paign. 

Perhaps  the  most  important  lesson  is  the  necessity  of  protecting  infants 
and  children  from  infection  with  tubercle  bacilli,  so  far  as  possible.  It  may 
perhaps  have  occurred  to  you  that  if,  in  so  many  instances,  tlie  primary 
tuberculous  infection  dating  from  early  life  be,  as  it  has  been  called,  a 
"  beneficent  vaccination,"  we  should  not  be  overanxious  to  prevent  it.  In 
reply  to  this  argument  it  may  be  stated,  in  the  first  place,  that  experience 
indicates  that  we  hardly  need  concern  ourselves  with  this  matter  of  securing 
protection.  We  are  not  likely  to  escape,  if  we  would,  the  minimal  tubercu- 
lous infections.  "  Am  Ende  bekommt  jeder  ein  bischen  Tuberkulose,"  as 
the  old  German  physician  said  many  years  ago.  The  preventive  vaccinations 
will  take  care  of  themselves. 

On  the  other  hand,  as  I  have  mentioned,  the  forms  of  tuberculosis  which 
appear  in  the  first  two  or  three  years  of  life  are  predominantly  fatal  forms, 
and  not  innocuous  vaccination  and  these  surely  we  should  do  all  in  our 
power  to  prevent.  Furthermore,  there  is  much  in  support  of  the  view  that 
the  ultimate  fate  of  the  individual  as  regards  progressive  tuberculosis,  it 
may  be  later  in  life,  depends  largely  upon  the  extent  of  the  primary  infec- 
tion, which  is  itself  related  to  the  number  and  virulence  of  the  bacilli  re- 
ceived into  the  body. 

In  the  light  of  our  newer  knowledge  there  is  abundant  reason  for  the  ever- 
increasing  emphasis  placed  upon  the  importance  of  attacking  the  problem 
of  tuberculosis  in  the  early  years  of  life.  The  key  note  is  the  segregation  of 
patients  with  open  tuberculosis,  that  is,  in  the  main,  the  consumptive,  so  that 
they  will  not  be  the  means  of  .spreading  the  infection  to  other  members  of 
the  family,  especially  the  children.  In  France  much  is  done  in  the  way  of 
removal  of  children  from  homes  where  there  is  a  consumptive  member,  but 
while  this  procedure  is  efi'ective,  and  perhaps  can  be  employed  oftener  in 
this  country  than  is  now  customary,  it  is  not  likely  to  be  widely  applicable 
with  us.  The  results  of  constructing  tenements  especially  adapted  for  the 
home  treatment  of  consumptives  must  await  further  trial  before  we  are 
warranted  in  drawing  conclusions  as  to  the  efficacy  of  this  interesting  experi- 
ment. Our  main  reliance,  as  has  been  so  often  urged  before  this  Associa- 
tion, must  be  upon  hospitals  designed  for  the  reception  of  advanced  or  open 
cases  of  tuberculosis,  and  it  would  appear  that  there  is  no  other  measure  of 
equal  importance  in  lessening  the  spread  of  the  disease. 

A  further  deduction  from  the  newer  views  as  to  the  pathogenesis  of  pulmo- 
nary consumption  is  the  importance  of  preventing  reinfections,  whether 
extraneous  or  autogenous,  and  of  maintaining  and  increasing  .the  resistance 
to  the  effects  of  such  reinfections.  Here  come  into  consideration  not  only 
44 


650  FREQUENT  TUBERCULOSIS  IX  EARLY  LIFE 

the  hospitals  for  the  care  of  tuberculous  patients,  but  all  those  procedures 
for  the  after  care  of  those  who  are  able  to  resume  work,  but  are  so  likely  to 
relapse  after  return  to  previous  conditions  of  living  and  work.  Working 
farms  and  colonies  for  the  tuberculous  have  an  important  place  in  the  com- 
paign  against  the  disease. 

I  believe  that  no  mistake  is  made  in  preaching  the  gospel  of  hygiene  to 
increase  resistance  to  tuberculosis.  Even  if  it  should  appear  that  undue 
emphasis  is  laid  upon  measures  of  general  hygiene  as  a  special  feature  of 
the  anti-tuberculosis  crusade — and  I  do  not  believe  that  such  is  the  case — 
the  incidental  benefits  in  furthering  the  cause  of  individual  and  public 
hygiene  and  the  general  improvement  of  the  health  of  the  people,  derived 
from  this  part  of  the  campaign,  have  been  of  incalculable  value.  It  has 
been,  above  all,  the  movement  against  tuberculosis  which  has  taught  people 
the  value  to  health  of  fresh  air,  of  proper  and  sufficient  food,  of  exercise  and 
play,  of  well  ventilated  and  sanitar}-  homes  and  workshops,  of  shorter  work- 
ing hours,  of  a  living  wage,  and  other  social  reforms. 

There  has  been  in  the  last  half  century,  and  especially  since  the  discovery 
of  the  tubercle  bacillus,  a  notable,  steadily  increasing  diminution  in  the 
amount  of  tuberculosis.  The  fact  that  this  decline  is  not  universal,  and 
that  where  it  has  occurred  it  has  been  in  varying  degrees  in  different  places, 
indicates  conclusively  that  special  causes  have  been  operative  in  bringing 
it  about.  I  believe  that  it  can  be  shown  that  the  reduction  stands  in  rela- 
tion to  the  character  and  efficiency  of  the  activities  directed  against  the  dis- 
ease, although  there  may  be  difficulty  in  assigning  to  each  factor  in  these 
activities  its  precise  share  in  the  result.  As  is  well  known,  Koch  and 
Newsholme,  after  careful  analyses  of  these  factors,  have  reached  the  con- 
clusion that  the  segregation  of  consumptives  in  hospitals  far  outweighs  in 
preventive  value  all  others. 

The  results  which  have  already  been  obtained  and  the  greater  ones  which 
we  can  reasonably  expect  to  follow,  both  in  the  control  of  tuberculosis  and 
in  the  improvement  of  the  health  and  efficiency  of  the  people,  are  full  of 
encouragement  to  press  forward  with  increasing  zeal  in  the  greatest  task 
ever  attempted  in  the  domain  of  preventive  medicine.  As  tuberculosis  is  a 
disease  of  society,  it  must  be  met  by  a  combination  of  all  the  forces  of  society, 
and  we  may  be  assured  that  such  combined  efforts,  intelligently  directed 
and  based  upon  accurate  knowledge,  will  bring  direct  and  indirect  benefits 
to  mankind  far  outweighing  all  tlie  money  and  time  and  energy  expended. 


CONTROL  OF  BOVINE  TUBEECULOSIS' 

It  is  clear  that  there  are  certain  matters  which  are  established ;  there  are 
others  which  are  very  much  in  dispute ;  and  still  others  which  we  must  regard 
as  hardly  approached  as  yet.  It  depends  a  good  deal  upon  where  we  lay  the 
emphasis.  We  may  agree  on  some  body  of  facts,  and  still  lay  emphasis  more 
upon  one  than  upon  the  other  feature,  and  we  may  reach  somewhat  different 
conclusions  without  disagreeing  as  to  the  facts. 

It  is  true  that  Koch  in  his  address  in  London  certainly  left  the  impression 
by  the  conclusion  drawn  from  his  own  words  that  there  was  practically  no 
danger  whatever  of  infection  from  bovine  sources.  It  is  true  also,  and  the 
point  has  been  emphasized  in  this  country,  that  Koch  did  not  add  very 
material  new  facts.  Dr.  Theobald  Smith,  one  of  the  most  careful  workers 
on  the  subject,  had  previously  pointed  out  the  rather  subtle  morphological 
and  biological  differences  between  the  human  voice  and  bovine  types.  He 
also  noticed  (it  was  known  before)  that  it  was  difficult  to  inoculate  success- 
fully calves  or  cattle  with  tubercle  bacilli  from  human  sources.  With  char- 
acteristic caution,  however,  he  did  not  venture  to  draw  the  conclusion  that 
because  calves  are  insusceptible,  relatively  to  human  tuberculosis,  we  should 
infer  that  human  beings  are  insusceptible  to  bovine  tubercle  bacilli.  That 
was  the  difference  mainly  between  Theobald  Smith's  and  Koch's  presentation 
of  the  subject.  Koch  drew  that  inference  without  basis  of  facts.  It  is  also 
true  that  Professor  Koch  at  the  Washington  Congress  somewhat  shifted  the 
position  he  had  previously  taken.  He  took  the  position  that,  in  the  campaign 
against  tuberculosis,  pulmonary  consumption  is  the  main  factor  to  be  con- 
sidered. I  think  he  stated  that  eleven-twelfths  of  the  deaths  from  tubercu- 
losis in  human  beings  were  traceable  to  pulmonary  tuberculosis;  that  the 
other  forms  of  tuberculosis — the  glandular,  the  surgical  forms  of  tuberculosis 
— were  not  open  cases ;  that  is,  they  did  not  figure  as  an  important  factor  in 
the  spread  of  disease;  therefore,  those  who  are  interested  in  tuberculosis  as 
a  problem  with  reference  to  tlie  extermination  of  the  disease  might  almost 
neglect  the  dangers  from  bovine  tuberculosis ;  that  it  was  upon  pulmonary 

*  Report  of  remarks  on  a  paper  of  Mazyck  P.  Ravenel  made  before  the  National 
Association  for  the  Study  and  Prevention  of  Tuberculosis,  Denver,  Col.,  June  21, 
1911. 

Nat.  Ass.  Study  &  Prev.  Tuberc,  Tr.,  Phila.,  1911,  VII,  367-370;  374. 

651 


653  CONTROL  OF  BOVINE  TUBERCULOSIS 

tuberculosis  we  should  concentrate  our  attention,  and  that  there  was  little  or 
no  evidence  of  infection  from  bovine  tuberculosis,  or  that  bovine  infection 
pla)''ed  no  particular  role  in  it.  Dr.  Park,  as  you  know,  has  come  to  the  same 
conclusion  at  which  Dr.  Ravenel  has  arrived  with  reference  to  the  role 
played  by  the  bovine  bacillus  in  the  causation  of  phthisis.  There  have  been 
a  few  cases  in  which  it  is  claimed  the  bovine  tubercle  bacillus  has  been  found 
in  phthisis,  chiefly  in  the  sputum.  I  know  that  Professor  Koch  considered 
that  the  most  important  thing,  at  present,  was  further  investigation  on  that 
subject.  He  called  attention  to  certain  important  sources  of  error,  in  butter 
and  milk,  where  the  bovine  tubercle  bacillus  was  present.  One  might  readily 
have  in  the  sputum  the  presence  of  the  bovine  tubercle  bacillus  accidentally, 
and,  at  the  same  time,  playing  no  part  whatever  in  the  disease  process  in  the 
lung;  therefore,  it  requires  much  more  than  mere  demonstration  of  the 
tubercle  bacillus  of  bovine  type  in  the  sputum  of  consumptives  before  one 
could  draw  the  inference  that  it  was  really  causing  the  disease  in  the  lung. 
I  happen  to  have  had  the  good  fortune  to  spend  an  hour  with  Professor 
Koch,  in  the  Institute  for  Infectious  Diseases,  a  year  before  he  died,  after 
he  had  returned  to  Berlin  from  America  and  I  found  him  engaged  almost 
exclusively  in  the  study  of  this  subject.  He  must  have  collected  a  good  deal 
of  material  and  new  facts.  I  have  heard  nothing  about  any  prospect  of  these 
being  published.  He  showed  me  figures  and  charts,  all  in  confirmation  of 
his  previous  position,  that  the  bovine  tubercle  bacillus  played  no  part  in  the 
production  of  pulmonary  tuberculosis ;  that  is  on  the  assumption  that  there 
is  no  transformation  of  the  bovine  into  the  human  type.  Of  course  there  is 
the  point  at  issue.  Koch  believed  there  was  no  such  transformation.  That 
is  the  opinion  very  cautiously  expressed  by  Dr.  Theobald  Smith,  and  I  do 
feel  that  his  position  on  anything  relating  to  this  question  is  almost  the  most 
authoritative  one  in  the  world ;  and  he  thinks  that  the  evidence  is,  to  say  the 
least,  ver}'  inconclusive ;  that  here  is  a  point  for  further  work,  and  research 
along  this  line  ought  to  be  fQllowed  out.  There  have  been  a  few  scattered 
observations.  An  attempt  has  been  made  to  determine  whether  or  not  the 
bovine  tubercle  bacillus  is  transformed  into  the  human  type  in  human  beings, 
namely,  by  studying  those  light  necrophilic  warts  so  commonly  seen  on  the 
hands  of  butchers,  to  try  to  find  out  whether  they  contained  the  bovine  type 
of  tubercle  bacilli.  There  is  nothing  easier  tlian  to  get  such  material  on 
which  to  work.  These  warts  remain  on  the  hands  of  butchers  for  a  consider- 
able time,  and  if  one  could  get  the  history  of  a  number  of  years,  and  has  a 
chance  of  using  that  material,  the  results  of  sucli  investigations  might  be 
valuable.  1  tbink  it  ought  to  l)e  had  in  great  abundance  in  ('hicago.  We 
must  have  opportunities  of  studying  these  warts  and  seeing  whether  wc  get 


CONTROL  OF  BOVINE  TUBERCULOSIS  653 

a  transformation  ©f  this  type  of  bacillus.  One  investigator  has  come  to  the 
conclusion  from  considerable  clinical  examination  that  there  was  such  a 
transformation  of  the  tubercle  bacillus,  with  apparent  preservation  of  viru- 
lence, indicating  that  the  bovine  type  was  due  to  the  fact  that  the  animal 
had  spontaneous  infection  from  another  source.  That  case  has  been  analyzed 
and  the  proof  found  inconclusive.  These  are  more  or  less,  I  think,  facts  on 
which  there  can  be  general  agreement.  I  myself  am  disinclined  to  the  view 
which  Dr.  Ravenel  favors  as  to  the  transformation  of  type.  One  should  be 
open-minded  on  the  subject  and  consider  it  still  »iih  judice.  There  are  so 
many  sources  of  error  which  we  have  to  consider  in  connection  with  this  work. 
If  you  have  inoculated  a  cow  with  the  human  type  of  tubercle  bacillus,  what 
appears  to  be  a  transformation,  as  indicated  by  the  production  of  a  general- 
ized tuberculosis  in  the  calf,  is  really  the  result  of  your  experimental  inocu- 
lation, and  not  the  result  of  spontaneous  infection.  That  is  a  difficult  matter 
to  control.  Mr.  Stiles  has  stated  most  impressively  his  views  on  this  subject, 
giving  us  a  series  of  fatal  cases,  making  a  very  notable  percentage,  to  say  the 
least,  of  fatal  cases  of  tuberculosis  in  human  beings,  chiefly  in  children.  If 
you  let  these  cases  run  they  will  doubtless  play  an  important  role  in  the 
spread  of  the  disease  from  person  to  person,  and  they  are  of  significance  from 
every  point  of  view,  particularly  from  a  humanitarian  standpoint. 

Shall  we  do  anything  to  check  that  large  mortality?  I  think  one  can 
accept  all  the  facts  which  Koch  himself  admitted  at  Washington,  and  still 
maintain  that  it  is  of  importance  to  recognize  that  there  is  a  serious  danger 
from  the  infection  of  human  beings  from  the  milk  of  tuberculous  cattle,  and 
that  while  Imi  lan  sources  are  far  more  important  in  the  spread  of  the  disease, 
we  should  not  by  any  means  neglect  the  other.  The  character  of  evidence 
which  Mr.  Stiles  has  brought  forward  here  is  one  deserving  of  every  respect, 
and  more  especially  by  physicians,  who  do  not  have  to  discuss  some  of  these 
more  subtle  laboratory  points.  Koch  himself  realized  that  in  his  London 
address  he  took  the  position  that  there  was  very  little  evidence  of  primary 
alimentary  infection.  There  are  extraordinary  differences  as  to  the  incidence 
of  tuberculosis  according  to  locality.  To  bring  that  into  exact  relation  with 
the  milk  supply  has  been  difficult.  While  the  experience  of  Edinburgh  which 
Mr.  Stiles  has  presented  is  very  important  and  apparently  conclusive  on  the 
points  he  has  brought  before  us,  still  in  Kiel  and  in  Vienna  they  claim  they 
have  scarcely  any  primary  intestinal  tuberculosis,  and,  of  course,  we  are 
infornied  by  Kitasato  that  in  Japan,  where  milk  in  not  used,  and  where  there 
is  little  or  no  tuberculosis  among  cattle,  they  have  the  same  types  of  glandu- 
lar and  bone  and  joint  tuberculosis,  and  we  can  exclude  positively  the  milk. 
These  statistics  we  find  are  interested  somewhat  differently.    However,  the 


654  CONTROL  OF  BOVINE  TUBERCULOSIS 

high  percentage  of  deaths  mentioned  by  Mr.  Stiles  teaches  us  the  great  im- 
portance of  such  clinical  facts  as  he  has  brought  before  us,  so  that  my  opinion 
is  that  we  are  justified  in  insisting  upon  a  better  control  of  the  purity  of  the 
milk  in  our  cities.  It  is  the  great  sanitary  problem  of  today.  It  is  a  great 
white  river,  and  it  is  just  as  much  a  river  as  the  water  flowing  through  our 
cities,  but  it  is  much  more  difficult  to  keep  pure  this  great  white  river  of 
milk.  It  is  just  as  important,  nevertheless,  and  the  most  urgent  problem 
before  our  municipal  health  authorities  today  is  the  protection  of  the  milk 
supply. 

I  will  say  that  there  is  little  or  no  value  attached  to  the  method  of  differen- 
tial diagnosis  which  Detre  advised. 


CHILD  WELFARE' 

Mr.  President,  Ladies  and  Gentlemen. — I  may  perhaps  be  permitted,  as  a 
resident  of  this  city,  to  reinforce  the  words  of  welcome  which  have  already 
been  expressed,  and  I  know  that  I  speak  in  behalf  of  my  fellow  citizens,  who 
are  also  present,  these  words  of  welcome,  to  the  members  of  this  Association, 
to  the  guests  and  others  who  have  been  so  good  as  to  come  here.  We  wish 
especially  to  express  our  gratitude  to  his  Eminence,  the  Cardinal;  to  his 
Excellency,  Ambassador  Jusserand,  who  has  brought  us  these  kind  messages 
from  France;  and  to  Professor  Fisher,  who  has  made  himself  an  inspiring 
leader  of  the  great  movement  for  the  improvement  of  public  health  in  this 
country;  and  I  would  like  especially  to  impress  the  note  of  welcome  to  my 
old  master  and  teacher  and  friend  of  these  many  years.  Professor  Jacobi,  of 
New  York. 

We  are  very  glad,  indeed,  to  have  this  first  meeting  of  an  Association,  which 
I  believe  initiates  one  of  the  most  important  campaigns  in  preventive  medi- 
cine in  this  country,  in  this  city,  partly,  perhaps,  because  there  is  no  city 
which  needs  the  influence  and  benefits  which  will  come  from  the  work  of  this 
Association  more  than  the  City  of  Baltimore;  partly,  also,  because  we  have 
a  certain  measure  of  loyal  pride  in  the  fact  that  that  great  tuberculosis  asso- 
ciation. The  National  Association  for  the  Study  and  Prevention  of  Tuber- 
culosis— which,  I  judge,  the  name  of  this  Association  has  followed — had  its 
first  meeting  in  this  city,  and  in  connection  with  it  was  an  exhibition  which 
Dr.  Fulton  devised  and  which  has  turned  out  to  be  one  of  the  most  interest- 
ing and  important  factors  in  the  whole  crusade  against  tuberculosis.  And 
I  trust  that  there  is  a  future  of  lasting  usefulness  and  power  before  this 
Association  equal  to  that  which  has  been  demonstrated  to  have  been  the 
outcome  of  the  work  accomplished  already  in  these  few  years  by  the  Tuber- 
culosis Association. 

There  is,  of  course,  no  need  of  my  saying  anything  more  than  has  already 
been  said  as  to  the  fundamental  importance  of  the  subject  of  infant  mor- 
tality. Statistics  are  tiresome  for  most  people,  but,  trite  as  it  may  be,  it 
certainly  is  enough  to  arrest  one's  attention,  no  matter  how  busy  he  may  be, 
to  learn  that  in  the  state  of  Maryland  over  one-fifth  of  all  the  deaths  of  all 
ages  occur  under  one  year  of  age;  that  one-third  of  all  the  deaths  occur 

^  Report   of   an  address   delivered  before   the  American  Association    for   the 
Study  and  Prevention  of  Infant  Mortality,  Baltimore,  November  9,  1910. 
Tr.  Am.  Ass.  Study  &  Prev.  Inf.  Mortal.,  Bait.,  1910,  I,  51-56. 

655 


656  CHILD  WELFAEE 

under  five  years  of  age.  The  rate  is  a  little  higher  in  this  state  in  conse- 
quence of  our  negro  population  than  in  some  other  parts  of  our  country. 
In  the  registration  area  of  this  country  the  deaths  under  one  year  of  age  are 
a  little  less  than  one-fifth  of  all  deaths  at  all  ages,  and  about  one-third  under 
five  years  of  age.  In  the  first  three  months  of  life,  one-ninth  of  all  the  deaths 
occur.  Such  figures  as  these  are  enough,  of  course,  to  indicate  the  funda- 
mental importance  of  this  subject. 

"WTien  one  inquires  into  the  leading  causes  of  death  during  this  period 
one  finds  that  the  greater  number  are  operative  in  the  first  months  of  life. 
Some  of  these  are  sometimes  spoken  of  as  unavoidable,  but,  as  Dr.  Jacobi 
has  .said,  most  of  them  are  not.  We  do  not  think,  however,  that  the  crusade 
in  the  prevention  of  infant  mortality  will  yield  the  quickest  results  if  directed 
against  those  causes  which  to  some  seem  unavoidable — such  causes  as  pre- 
mature births,  congenital  defects,  hereditary  taints,  accidents  at  birth, 
causes  of  that  kind.  It  is  more  especially  against  another  set  of  causes  of 
infant  mortality,  namely,  the  so-called  diarrhoeal  and  digestive  disorders, 
the  acute  respiratory  diseases,  bronchitis  and  pneumonia  and  the  infections 
that  the  campaign  should  be  directed.  Probably  the  infections  play  a  very 
important  part  in  the  digestive  disorders,  and  tuberculosis  we  know  plays  a 
by  no  means  unimportant  part  in  the  deaths  during  the  first  year  of  life. 
During  this  period,  especially  in  nurslings  the  infectious  diseases  which  we 
associate  with  childhood  are  less  common  than  after  the  first  year  of  life. 
Whooping  cough  and  measles  occur,  but  scarlet  fever  is  uncommon  and  this 
is  especially  true  among  those  that  are  nursed  at  the  breast.  This  is  in 
itself  suggestive ;  it  shows  that  the  infant  receives  from  the  mother  a  certain 
measure  of  protection  against  diseases  toward  which  she  is  herself  immune. 
There  are  many  reasons  why  the  cow's  milk  can  never  be  an  entirely  satis- 
factory substitute  for  the  mother's  milk,  and  one  reason  is  that  the  protective 
substances  in  the  cow's  milk — admirable  as  they  may  be  for  protecting  the 
calf  against  the  diseases  of  cattle — do  not  protect  the  infant  against  the 
diseases  of  the  human  being.  We  have  tlie  most  satisfactory  experimental 
evidences  that  the  milk  contains  immune  substances  which  have  been  gen- 
erated  in  the  body  of  the  mother,  and  see  how  important  it  is  that  she  should 
transmit  these  protective  substances  to  the  offspring  at  this  period  of  life 
when  the  offspring  is  attempting  to  adjust  itself  to  these  new  conditions  and 
is  exposed  to  all  these  changes.  This  kind  of  protection  is  needed  particu- 
larly in  the  class  of  diseases  which  I  have  specified,  the  acute  respiratory 
and  diarrlioeal  infections  and  the  infections  which  are  most  preventable. 
Professor  Fisher  has  made  interesting  investigations,  which  he  himself 
would  not  consider  to  be  anything  any  tiling  more  than  approximate,  but 
they  are  certainly  suggestive  as  to  what  is  the  ratio  of  preventability  of  these 
various  diseases  of  childhood  and  infancy.    At  least  60  per  cent  of  this  class 


CHILD  WELFARE  657 

of  diseases  is  preventable,  and  readily  preventable,  by  the  application  of 
knowledge  already  in  our  possession.  With  further  additions  to  knowledge, 
the  ratio  of  preventability  would  be  still  further  increased,  but  at  present 
we  probably  are  within  entirely  safe  bounds  to  say  that  60  per  cent  of  the 
deaths  of  infants  in  the  first  year  of  life  due  to  the  causes  which  I  have 
mentioned  could  be  prevented. 

It  will  be  the  purpose  of  this  Association  to  point  out  in  considerable 
detail  what  the  causes  of  these  preventable  diseases  are  and  the  measures 
which  are  to  be  taken  for  prevention.  One  cannot  have  the  most  cursory 
reference  to  the  subject  of  infant  mortality  without  having  at  once  brought 
to  one's  attention  the  fundamental  importance  of  material  nursing  in  pre- 
serving the  life  of  the  infant.  That  will  be  repeated  over  and  over  again.  I 
think  that  those  in  the  audience  who  are  familiar  with  the  subject  only  in^ 
the  families  of  the  well-to-do  can  hardly  realize  the  risks  in  artificial  feeding. 
It  is  not  because  artificial  feeding  is  not  possible.  It  is  possible  we  all  know, 
but  it  requires  an  amount  of  care  and  education  on  the  part  of  those  entrusted 
with  it  which  is  not  to  be  expected  in  the  families  of  the  poor.  It  is  not 
surprising  to  hear  that  the  deaths  are  at  least  15  to  1  among  the  artificially 
fed,  as  compared  with  those  fed  at  the  breast. 

Our  time  for  keeping  you  here  has  passed,  but  before  closing  I  would  like 
to  point  out  what  I  conceive  to  be  certain  of  the  useful  functions  of  this 
Association.  Of  course,  one  of  the  most  important  is  the  education  of  the 
public,  the  enlightenment  of  the  public.  The  responsibility  is  with  you; 
it  is  with  me ;  it  is  with  tlie  public.  When  one  is  told  that  the  application 
of  knowledge  which  we  now  possess  in  an  entirely  practicable  manner  will 
lead  to  the  saving  of  125,000  lives  yearly  among  these  infants,  is  that  not 
enough  to  stir  one  to  activity  ?  In  this  country  at  least — in  any  democratic 
country — the  public  must  be  enlightened,  otherwise  we  cannot  secure  from 
our  legislatures  the  necessary  laws  and  the  necessary  funds,  resources  for 
carrying  out  these  preventive  measures.  I  regard,  therefore,  the  stirring  up 
of  the  public,  the  enlightenment  of  the  public,  as  one  of  the  most  important 
functions  of  the  Association.  It  should  stimulate  better  sanitary  organiza- 
tion and  administration  in  the  country  all  along  the  line.  It  should  lend  its 
whole  force  toward  the  organization  of  a  National  Health  Department,  which 
movement  has  been  so  forcibly  presented  to  ns  by  Professor  Fisher  tonight. 
We  should  all  be  familiar  with  the  character  of  the  opposition  to  the  move- 
ment. I  do  not  propose  to  discuss  it,  but  it  is  based  upon  misconception 
and  it  is  based  upon  ignorance,  and  sometimes,  I  think,  it  is  based  upon 
intentional  misrepresentation,  as  has  been  pointed  out,  putting  personal  in- 
terests and  commercial  interests  above  the  interests  of  health  and  life.  This 
Association,  therefore,  should  stand,  for  a  strengthening  of  the  activities 
of  the  Federal  Government  in  public  health  work.    That  department  will 


658  CHILD  WELFARE 

* 

surely  have  a  Department  of  Child  Hygiene.  We  have  had  demonstrated  to 
us  in  New  York  City  how  much  good  can  be  accomplished  by  the  creation 
in  a  Department  of  Health  of  a  division  of  Child  Hygiene.  They  have  taken 
the  lead  there  in  this  regard  as  so  often  and  to  such  a  great  extent  in  public 
health  work. 

The  question  of  registration  of  births  is  at  the  bottom  of  this  whole  move- 
ment. I  hope  those  who  are  here  will  be  able  to  be  present  when  Dr.  Wilbur 
reads  his  paper  on  this  subject  tomorrow  night.  Then  you  will  learn  that 
we  are  creeping  in  the  dark  until  we  have  an  accurate  and  tolerably  full 
registration  of  births.  There  must  be  a  pressure  brought  to  bear  upon  the 
medical  profession,  who  are  woefully  lacking  in  the  performance  of  their 
duty  in  this  matter,  and  I  simply  mention  that  it  is  a  matter  of  very  first 
importance  to  be  considered  in  the  activities  of  this  Association  to  see  that 
our  country  is  no  longer  in  the  scandalous  and  disgraceful  condition  in  which 
it  is  today  as  regards  an  accurate  recording  of  births.  It  would  be  the  topic 
of  an  entire  lecture  to  make  clear  to  you  exactly  why  we  should  have  an 
accurate  registration  of  births.  Until  there  is  such  a  registration  one  cannot 
tell  what  the  rate  of  infant  mortality  is,  the  ratio  of  deaths  of  infants  under 
1  year  of  age  per  thousand  living.  One  can  only  guess  at  it.  One  cannot 
define  the  rate  of  infant  mortality  at  all  in  this  country  today.  One  esti- 
mates it  is  something  like  one-seventh ;  in  New  York  perhaps  one-seventh 
of  those  born  die  in  the  first  year  of  life. 

Another  very  important  activity  will  be  the  correlation  of  all  the  various 
agencies  that  are  acting  separately.  The  various  public  and  private  agencies 
should  be  all  brought  together  in  order  to  secure  the  best  results,  because 
they  will  often  be  working  at  cross  purposes  otherwise.  This  is  specified  as 
one  of  the  very  important  activities  of  the  Association,  and  it  is  indeed  to 
be  very  much  emphasized. 

Then  I  hope  the  Association  will  stimulate  investigation  in  this  field.  We 
have  by  no  means  the  amount  of  knowledge  which  is  to  be  desired.  It  is  a 
big  and  significant  fact  that  the  campaign  for  the  prevention  of  infant 
mortality  has  been  long  delayed  in  this  direction.  One  reason  is,  I  think, 
that  we  have  not  such  tangible,  accurate  or  precise  knowledge  of  the  many 
causes  of  infantile  diseases  that  we  have  about  some  other  diseases.  Take, 
for  instance,  yellow  fever,  typhoid,  malaria.  How  relatively  definite  our 
knowledge  is  of  the  etiology.  There  are  a  great  many  problems  connected 
with  this  entire  subject,  which  must  be  solved  before  we  can  go  ahead  with 
as  full  knowledge  as  is  to  be  desired. 

I  think  also  one  of  the  important  purposes  of  the  Association  must  be  to 
formulate  a  definite  program  of  preventive  measures.  When  one  goes  over 
all  the  possible  factors  and  influences  concerned,  one  will  find  that  one  is 
brought  to  problems  of  poverty,  of  ignorance,  of  dirt,  of  insanitation,  of  in- 


CHILD  WELFARE  659 

dustrial  conditions,  etc.,  and  one  is  confused  to  know  exactly  where  to  take 
hold  in  order  to  secure  in  tlie  shortest  time  the  best  results.  I  hope  one  of 
the  purposes  of  this  Association  will  be  to  formulate  as  definite  a  program 
as  possible  as  to  where  and  how  efforts  should  be  concentrated  in  order  to 
secure  the  best  results  in  the  shortest  time  and  in  the  most  economical  way. 

These  are  what  I  conceive  to  be  among  the  important  functions  of  this 
Association.  What  one  may  expect  from  the  direct  benefit  in  the  saving  of 
human  life  would,  of  course,  justify  all  efforts ;  but  I  am  very  fond  of  dwell- 
ing upon  the  indirect  benefits  which  come  from  all  these  movements.  "  In- 
fant mortality  is  the  most  sensitive  index  of  social  welfare  " ;  it  takes  hold 
of  the  very  foundations  of  society.  Its  prevention  means  improvement  in 
the  homes,  improvement  in  tlie  mothers,  and  improvement  in  the  social  con- 
ditions, the  industrial  conditions  and  the  sanitary  conditions  in  general. 
This,  as  Professor  Fisher  has  pointed  out,  is  sufficient  answer  to  those  near- 
sighted persons  who  think  they  are  extremely  philosophical  in  this  matter 
when  they  argne  that  we  are  interfering  with  natural  selection.  News- 
holme,  who  is  the  greatest  student  of  this  whole  subject,  at  least  from  a 
statistical  point  of  view,  says  the  high  rate  of  infant  mortality  brings  about 
conditions  which  make  for  national  degeneracy  and  infirmity,  and  I  believe 
firmly  that  this  is  true.  Those  who  plead  that  our  preventive  efforts  are  in- 
terfering with  the  natural  selection  of  the  individual  are  pleading  virtually 
for  the  retention  of  what  are  the  most  unfortunate  social  conditions.  They 
are  pleading  that  the  woman  shall  continue  to  work  in  factories  to  the  end 
of  her  pregnancy.  They  are  pleading  for  continuance  of  the  intolerable 
social  conditions.  I  think  we  can  look  forward,  even  if  this  Association 
meets  only  a  part  of  its  expectations  of  what  it  is  going  to  accomplish  in 
this  country,  to  a  great  future  of  usefulness,  both  of  direct  and  indirect 
benefit. 

Let  me  urge  upon  you  the  importance  of  studying  the  exhibit.  I  have 
not  myself  had  the  opportunity  to  do  so  yet,  but  I  know  that  that  exhibit  has 
been  brought  together  with  great  sacrifice  of  time  and  thought  and  energy 
on  the  part  especially  of  the  Chairman  of  the  Committee,  Dr.  Price,  Secre- 
tary of  the  State  Board  of  Health.  We  are  particularly  indebted  to  Dr. 
Schereschewsky  of  the  Public  Health  and  Marine  Hospital  Service,  who 
has  been  of  invaluable  assistance  in  helping  us  to  get  together  this  exhibit. 
We  are  also  indebted  to  Dr.  Wilbur,  head  of  the  Vital  Statistics  Department, 
Bureau  of  the  Census,  and  to  many  others,  who  have  been  so  good  as  to  send 
exhibits.  No  such  exhibit  has  ever  been  brought  together  before.  It  will  be, 
I  think,  the  most  distinctive  and  instructive  feature  of  this  meeting,  and  I 
believe  it  will  be  an  example  to  those  who  are  engaged  in  similar  movements 
elsewhere  and  that  they  will  recognize  this  feature  as  their  strongest  means 
of  reaching  efficiently  the  general  public. 


INSTITUTE  OF  HYGIENE' 

At  a  conference  *  on  training  for  public  health  service  held  at  the  offices 
of  the  General  Education  Board  in  New  York  on  October  16,  1914,  dis- 
cussion seemed  to  develop  substantial  agreement  on  the  following  points: 
(1)  That  a  fundamental  need  in  the  public  health  service  in  this  country  at 
the  present  time  is  of  men  adequately  trained  for  the  work;  (2)  that  a  dis- 
tinct contribution  toward  meeting  this  need  could  be  made  by  establishing 
at  some  convenient  place  a  school  of  public  health  of  high  standard;  (3)  that 
such  an  institution,  while  maintaining  its  separate  identity,  should  in  the 
interest  both  of  economy  and  of  efficiency  be  closely  affiliated  with  a  univer- 
sity and  its  medical  school;  (4)  that  the  nucleus  of  this  school  of  public 
health  should  be  an  institute  of  hygiene, 

'Mr.  Rose  and  Dr.  Welch  were  asked  to  formulate  a  plan  for  such  an  insti- 
tute of  hygiene  and  in  compliance  with  this  request  offer  the  following 
report,  which  is  designed  to  set  forth  the  scope  and  general  character  of  the 
organization  of  the  institute  and  the  service  which  it  should  render  in  train- 
ing in  hygiene,  preventive  medicine  and  public  health  and  in  the  advance- 
ment of  these  subjects.  If  desired,  the  report  can  be  supplemented  by  a 
detailed  statement  of  organization,  plan  of  building,  budget  and  courses  of 
instruction. 

I.  Public  Health  and  Hygiene  in  England  and  in  Germany 

The  origins  of  the  modern  public  health  movement  and  of  the  cultivation 
of  hygiene  as  an  independent  science  may  be  found  especially  in  the  passage 
of  the  Public  Health  Act  in  England  in  1848  and  in  the  establishment  of  tlie 
first  hygienic  institute  by  von  Pettenkofer  in  Munich  in  1865.  The  greatest 
stimulus  to  further  development  ctame  from  the  discoveries  relating  to  the 
causation  and  the  mode  of  spread  of  the  infectious  diseases  and  the  conse- 

>  William  H.  Welch  and  Mr.  Wickliffe  Rose. 

The  following  report,  prepared  by  Dr.  William  H.  Welch  and  Mr.  Wickliffe 
Rose,  was  presented  to  the  Trustees  at  their  meeting,  January  12,  1916.  The 
Rockefeller  Foundation  Annual  Report,  (The  Rockefeller  Foundation,  61  Broad- 
way, New  York),  1916,  p.  415-427. 

'  Dr.  A.  C.  Abbott,  Dr.  Hermann  M.  Biggs,  Dr.  Simon  Flexner,  Mr.  Jerome  D. 
Greene,  Dr.  Victor  G.  Heiser,  Dr.  Edwin  O.  Jordan,  Mr.  Starr  J.  Murphy,  Dr.  Wm. 
H.  Park,  Mr.  Wickliffe  Rose,  Dr.  M.  J.  Rosenau,  Dr.  Theobald  Smith,  Dr.  George 
C.  Whipple,  Dr.  C.  E.  A.  Winslow,  Dr.  Wm.  H.  Welch,  Prof.  D.  D.  Jackson,  Dr. 
F.  Cleveland,  Dr.  Wallace  Buttrick,  Dr.  E.  C.  Sage  and  Dr.  Abraham  Flexner, 
660 


INSTITUTE  OF  HYGIENE  661 

quent  vastly  increased  power  to  control  these  diseases.  It  is  instructive  for  the 
present  purpose  to  note  the  different  conceptions  and  directions  of  develop- 
ment in  this  field  in  the  two  countries.  In  Germany  every  university  has  its 
department  or  institute  of  hygiene,  conducted  by  a  professor  and  corps  of 
assistants,  where  the  subject  is  presented  broadly  in  all  its  varied  aspects, 
students  are  taught  by  lectures,  laboratory  courses  and  field  work,  and  the 
science  is  advanced  by  research.  In  England,  on  the  other  hand,  the  impor- 
tant hygienic  laboratories  are  few  and  mostly  governmental  or  independent. 
For  training  the  emphasis  is  laid  upon  public  health  administration,  in  which 
respect  Great  Britain  leads  the  world.  Those  desiring  to  qualify  as  medical 
officers  of  health  must  possess  the  diploma  in  public  health,  obtained  by 
passing  an  examination  after  at  least  nine  months  of  specal  preparation,  most 
frequently  under  a  qualified  medical  officer  of  health  and  in  a  hospital  for 
infectious  diseases.  It  seems  obvious  that  lessons  are  to  be  learned  from  both 
the  German  and  the  English  systems,  and  that  the  ideal  plan  will  give  due 
weight  to  both  the  scientific  and  the  practical  aspects  of  hygiene  and  public 
health. 

II.  The  Situation"  and  Needs  in  Ameeica 

In  this  country  we  are  woefully  lacking  both  in  laboratories  of  hygiene  and 
in  opportunities  for  training  in  public  health  work.  Three  or  four  medical 
schools  have  hygienic  laboratories,  but  none  is  complete,  and  adequately 
equipped  and  supported.  Still  other  schools  attempt  something  in  the  way 
of  instruction  in  this  subject,  but  it  is  all  inadequate  and  unsatisfactory. 

The  need  for  supplying  these  deficiencies  is  at  present  the  most  urgent  one 
in  medical  education  and  in  public  health  work,  and  is  recognized  on  all  sides. 
The  cry  comes  loudest  from  public  health  officials,  social  workers  and  others 
interested  in  public  health  administration,  national,  state,  municipal  and 
rural,  who  realize  the  lack  of  trained  leaders  and  trained  workers  in  all  grades 
of  the  service.  Here  with  the  rapidly  growing  appreciation  of  efficient  public 
health  organization  new  and  promising  careers  of  useful  service  are  opening 
for  those  who  are  qualified  by  ability,  character  and  training.  Scarcely  less 
important  is  it  for  medical  students  and  physicians  M^ho  engage  in  practice 
to  be  well  grounded  in  the  principles  of  hygiene  and  of  preventive  medicine. 
Furthermore,  the  advancement  of  knowledge  in  this  field,  the  cultivation  of 
hygiene  as  a  science,  is  one  of  the  great  needs  of  this  country  and  should  be  a 
fundamental  aim  of  an  institute  of  hygiene. 

III.  Various  Classes  to  be  Trained 

The  first  and  in  many  respects  the  most  important  class  of  persons  who 
will  seek  to  be  trained  in  a  school  of  public  health  are  those  who  expect  to 
devote  their  lives  to  health  work  in  some  of  its  branches.    These  will  aim  to 


662  INSTITUTE  OF  HYGIENE 

become  for  the  most  part  public  health  officials  or  to  be  engaged  in  some 
capacit}'  in  public  health  service,  but  some  may  become  teachers  or  be  con- 
nected with  institutions  or  find  other  opportunities  for  a  career  in  the  ever 
widening  field  of  sanitation.  It  is  of  the  first  importance  to  consider  and  to 
supply  the  needs  for  the  education  of  the  prospective  public  health  officials. 
Without  attempting  an  exhaustive  analysis,  the  following  classification 
will  suffice  to  indicate  the  various  types  of  officers  or  experts  required  in  public 
health  administration : 

1.  Higher  administrative  officials,  as  commissioners  of  health  and  health 
officers  in  cities  and  districts,  and  division  or  bureau  chiefs  in  the  larger 
state  and  city  departments  of  health. 

2.  Health  officers  in  towns,  villages  and  rural  communities. 

3.  Higher  technical  officials  or  experts,  as  statisticians,  sanitary  engineers, 
chemists,  bacteriologists,  diagnosticians,  epidemiologists,  etc. 

4.  Inspectors  of  various  kinds,  as  school,  sanitary,  food,  factory,  etc. 
inspectors. 

5.  Public  health  nurses. 

With  this  class  may  be  included  those  preparing  to  enter  the  Public  Health 
Service  of  the  federal  government. 

An  institute  or  school  of  hygiene  should  furnish  suitable  training  for  all 
of  these,  and  while  courses  adapted  for  special  needs  will  be  supplied,  it  does 
not  seem  desirable  to  conceive  of  such  an  institute  as  constituted  primarily  to 
provide  training  for  higher  or  lower  grades  of  service  so  much  as  to  furnish 
opportunities  for  a  good  general  education  in  all  branches  of  hygiene. 

Wiiile  it  is  hardly  possible  to  over  estimate  the  importance  of  providing 
opportunities  for  the  training  of  those  who  are  to  become  public  health 
officials,  the  need  here  is  at  present  so  acute  that  there  is  some  danger  of 
overlooking  the  conception  of  hygiene  as  a  science  and  art  which  is  much 
broader  than  its  application  to  public  health  administration.  Hygiene  in- 
cludes much  more  than  state  medicine.  It  is  not  necessary  to  consider  here 
the  distinction  sometimes  made,  especially  in  this  country,  between  hygiene 
and  sanitation.  In  this  report  the  term  "  hygiene  "  is  used  to  include  both, 
that  is,  the  whole  body  of  knowledge  and  its  application  relating  to  the 
preservation  and  improvement  of  health  of  individuals  and  of  the  community 
and  to  the  prevention  of  disease. 

With  this  broad  conception  it  is  obvious  that  the  ediicational  and  scientific 
opportunities  of  an  institute  of  hygiene  should  not  be  limited  to  the  use  of 
those  who  intend  to  become  specialists  in  public  health  work  and  should  cover 
a  wider  field  than  that  of  state  medicine  or  sanitation. 

It  is  of  the  utmost  importance  that  education  in  the  principles  of  hygiene 
should  be  available  for  students  and  graduates  in  medicine  who  are  to  engage 


INSTITUTE  OF  HYGIENE  663 

in  the  practice  of  their  profession.  With  the  present  crowded  medical  cur- 
riculum obligatory  courses  in  hygiene  for  undergraduate  students  of  medi- 
cine must  necessarily  be  restricted,  but  with  the  tendency  toward  greater 
freedom  of  election  of  medical  studies  there  is  the  need  and  opportunity  to 
provide  more  extensive  optional  courses  in  hygiene.  There  is  a  wide  field 
for  the  establishment  of  graduate  courses  in  hygiene  for  physicians.  Even 
in  Great  Britain,  where  the  character  of  training  is  designed  almost  wholly 
for  public  health  officials,  many  who  intend  to  become  medical  practitioners 
secure  the  diploma  in  public  health.  The  mission  of  the  practising  physician 
is  in  many  respects  changing,  and  there  can  be  no  doubt  that  a  year  or  more 
of  graduate  work  in  hygiene  would  be  eagerly  sought  by  many  physicians  and 
and  would  greatly  increase  their  capacity  of  useful  service  to  their  patients 
and  to  the  community,  if  the  proper  opportunity  for  such  work  were  provided. 

Sanitary  engineering  has  become  a  specialized  profession,  and  the  institute 
of  hygiene  should  combine  with  tlie  engineering  school  in  supplying  the 
requisite  training. 

The  public  health  nurse,  both  as  a  part  of  the  public  health  service  and 
independently  of  such  connection,  is  destined  to  play  a  role  of  increasing 
importance  in  the  improvement  of  conditions  of  health  living  and  working 
and  in  the  control  of  infectious  and  industrial  diseases  in  this  country.  The 
institute  of  hygiene  should  cooperate  with  schools  and  organizations  for 
training  nurses  in  meeting  the  need  for  a  supply  of  trained  public  health 
nurses. 

When  one  considers  the  many  points  of  contact  between  the  modern  social 
welfare  movement  and  the  public  health  movement,  and  to  what  an  extent 
social  and  economic  factors  enter  into  questions  of  public  health  it  is  clear 
that  an  institute  of  hygiene  must  take  full  cognizance  of  such  factors  and  that 
students  of  social  science  should  profit  by  certain  opportunities  in  the  insti- 
tute, as  well  as  students  of  hygiene  by  training  in  social  science  and  social 
work. 

An  important  class  to  be  provided  for  in  an  institute  of  hygiene  will  be 
those  engaged  in  special  advanced  work  in  some  branch  of  the  subject  and  in 
original  investigations  of  hygienic  problems.  A  main  function  of  the  insti- 
tute should  be  the  development  of  the  spirit  of  investigation  and  the  advance- 
ment of  knowledge,  upon  which  intelligent  public  health  administration  and 
individual  hygiene  are  absolutely  dependent.  It  will  be  especially  from  this 
class  of  advanced  workers  and  investigators  and  from  the  group  of  assistants 
in  the  institute  that  the  teachers  and  the  authorities  and  experts  in  hygiene 
will  be  recruited  for  service  in  different  fields  of  activity  and  the  standards 
of  the  profession  of  hygiene  and  of  public  health  will  be  elevated. 


664  INSTITUTE  OF  HYGIEXE 


IV.  Field  to  be  Covered 


The  field  covered  by  the  terms  *'  hygiene,"  '*  sanitary  science,"  "  public 
health,"  "  preventive  medicine  "  is  so  broad  and  varied  that  it  is  hardly  pos- 
sible within  a  brief  compass  to  indicate  all  of  the  subjects  here  included. 
Strictly  speaking  the  territory  embraces  a  group  of  sciences  or  the  application 
of  various  underlying  sciences.  Unity  is  to  be  found  rather  in  the  end  to  be 
accomplished — the  preservation  and  the  improvement  of  health — than  in  the 
means  es.sential  to  this  end.  It  is  the  focussing  upon  this  definite  purpose 
which  gives  coherence  to  the  organized  body  of  knowledge  embraced  under 
the  designations  "  hygiene "  and  "  sanitation,"  and  makes  important  its 
study  and  cultivation  as  a  professional  pursuit. 

Although  the  practitioner  should  have  knowledge  of  hygiene  and  of  the 
means  of  preventing  disease  and  has  abundant  opportunity  in  the  practice 
of  his  calling  to  apply  this  knowledge,  and  the  public  health  worker,  if  he  is 
to  prevent  disease,  must  have  a  knowledge  of  the  origin,  mode  of  spread  and 
diagnosis  of  disease,  still  it  is  becoming  increasingly  clear  that  public  healtli 
work  constitutes  a  distinct  profession,  and  the  wider  recognition  of  this  fact 
will  be  an  important  result  of  the  creation  of  institutes  or  schools  of  hygiene. 

The  wide  scope  of  the  professional  training  required  for  the  well  equipped 
public  health  worker  is  sufficiently  indicated  by  the  mere  enumeration  of  the 
more  important  subjects  to  which  more  or  less  attention  must  be  given  in  an 
institute  of  hygiene,  at  least  so  far  as  their  scientific  groundwork  in  relation 
to  sanitation  is  required.  Such  subjects  are  vital  statistics ;  epidemiology  or 
the  causation,  spread  and  prevention  of  transmissible  diseases,  including 
tuberculosis  and  the  venereal  diseases ;  diagnosis  of  infectious  diseases ;  indus- 
trial hygiene;  sanitar}-  parasitology,  including  bacteriolog}'  and  immunology; 
sanitary  chemistrv' ;  sanitary  engineering ;  hospital  construction  and  admini- 
stration ;  housing,  ventilation,  heating,  lighting ;  disinfection ;  the  hygiene  of 
air,  soil,  water  and  climate ;  water  supplies  and  sewage  disposal ;  infant  mor- 
tality and  child  hygiene ;  hygiene  of  schools ;  mental  hygiene ;  heredity  and 
eugenics;  social  hygiene;  personal  hygiene;  diet  and  nutrition;  rural,  farm 
and  dairy  hygiene;  milk  supply;  food  and  drug  adulterations;  nuisances; 
public  health  administration  and  organization,  sanitary  laws  and  codes ;  quar- 
antine and  immigration;  tropical  hygiene;  relation  of  animal  diseases  to 
human  diseases;  public  education  in  healthy  living;  social  service  work;  sani- 
tary surveys. 

V.  Agency  Requirkd  to  Perform  this  Functiox 

The  central,  essential  and  main  agency  required  to  meet  the  needs  which 
have  been  indicated  is  an  institute  of  hygiene,  housed  in  its  own  building, 
provided  with  the  requisite  laboratories  and  facilities  and  with  its  own  staff 


INSTITUTE  OF  HYGIENE  665 

of  teachers  giving  their  entire  time  to  the  work  of  teaching  and  investigating. 
Given  such  a  central  institute  it  is  easy  to  add  to  the  curriculum,  when 
found  necessary,  certain  courses  which  are  now  given,  or  could  readily  be 
supplied  by  various  existing  departments  of  the  medical  school,  the  engineer- 
ing school  or  other  faculties  of  the  university.  The  mere  assembling  of  such 
courses  does  not  constitute  a  school  of  hygiene.  The  great  need  of  the 
country  today  in  the  promotion  of  public  health  is  the  establishment  of  well 
equipped  and  adequately  supported  institutes  or  laboratories  of  hygiene, 
where  the  science  of  hygiene  in  its  various  branches  is  fruitfully  cultivated 
and  advanced  and  opportunities  are  afforded  for  thorough  training  in  both 
the  science  and  the  art.  It  would  be  a  misfortune  if  this  broader  conception 
of  the  fundamental  agency  required  for  the  advancement  of  hygienic  knowl- 
edge and  hygienic  education  should  be  obscured  through  efforts  directed 
solely  towards  meeting  in  the  readiest  way  existing  emergencies  in  public 
health  service. 

1.  Relation  to  a  Medical  School. — The  profession  of  the  sanitarian  or 
public  health  worker  not  being  identical  with  that  of  the  practitioner  of 
medicine,  the  institute  of  hygiene,  as  the  essential  part  of  a  school  of  hygiene, 
should  have  an  independent  existence  and  should  not  be  regarded  merely  as 
a  department  of  a  medical  school.  But  the  medical  school  offers  much  which 
the  institute  of  hygiene  will  require  either  as  preliminary  training  or  in 
course  and  which  it  will  not  care  to  duplicate.  In  the  interest  of  economy 
and  efficiency,  therefore,  the  school  of  hygiene  should  be  closely  related  to  a 
medical  school  of  high  standard  in  such  way  that  the  facilities  of  each  should 
be  open  to  the  students  of  both. 

It  is  likewise  important  for  study  and  training  in  preventive  medicine  that 
the  institute  should  have  access  to  the  facilities  of  a  good  general  teaching 
hospital,  as  well  as  to  various  special  hospitals.  The  need  of  opportunities 
for  observation  and  study  of  patients  in  an  infectious  disease  hospital  is  of 
course  obvious. 

2.  Connection  with  a  University. — To  perform  to  best  of  advantage  its 
function,  the  institute  should  be  a  part  of  a  university.  The  medical  school 
has  found  such  connection  to  be  a  practical  necessity.  The  institute  of  hy- 
giene would  draw  even  more  heavily  upon  certain  schools  or  departments  of 
the  .university,  as  those  of  engineering  and  of  sociology.  In  additon  to  having 
at  its  disposal  the  facilities  of  the  university,  the  institute  would  find  the 
stimulating  and  sustaining  scientific  spirit  and  ideals  of  the  university  an 
indispensable  asset. 

3.  Separate  Identity. — While  intimately  related  to  the  university  and  its 
medical  school,  the  institute  of  hygiene  should  be  established  on  its  own 

45 


666  INSTITUTE  OF  HYGIENE 

foundation,  and  should  preserve  and  emphasize  its  own  identity  as  a  separate 
institution  devoted  exclusively  to  the  science  and  the  service  of  health;  it 
should  have  its  own  building,  and  its  own  corps  of  instructors  with  adequate 
provision  for  teaching  and  research. 

While  it  is  not  difficult  to  bring  together  on  paper  a  group  of  courses 
selected  from  the  several  schools  and  departments  of  the  university  and  by 
the  addition  of  a  few  new  courses  make  a  presentable  prospectus  of  a  school 
of  public  health,  this  is  not  the  conception  of  such  a  school  or  institute  as  we 
believe  will  best  fulfill  the  functions  of  developing  the  science  and  art  of 
hygiene  and  of  training  for  this  new  profession.  If  the  institute  is  to  make 
itself  felt  as  a  constructive  force  it  must  have  in  it  a  group  of  scientific  inves- 
tigators and  teachers  whose  absorbing  interest  is  in  developing  the  science 
of  hygiene  and  applying  it  to  the  conservation  of  health. 

While  the  concentration  of  work  here  advocated  involves  some  duplication 
of  equipment,  this  is  not  as  large  as  might  be  supposed  and  in  view  of  the 
great  advantages,  does  not  constitute  a  serious  objection.  The  institute  must 
have  its  own  chemical  laboratory;  it  would  be  inconvenient  and  unsatisfac- 
tory in  the  extreme  to  attempt  to  use  chemical  laboratories  devoted  mainly 
to  other  purposes  for  the  many  important  studies  in  sanitary  chemistry.  The 
principle  microbiological  laboratory  of  a  medical  school  could  without  detri- 
ment be  transferred  to  the  institute  of  hygiene,  although  provision  must  exist 
for  bacteriological  work  in  the  pathological  laboratory,  as  well  as  in  the  hos- 
pital. Most  of  the  other  physical  equipment  of  the  institute  would  involve 
little  duplication. 

4.  Organization  and  Departments. — At  least  in  the  beginning  there  should 
be  a  director  of  the  institute,  who  will  also  be  the  head  of  one  of  the  main 
divisions.  Eventually  the  heads  of  these  divisions  may  constitute  a  group  or 
faculty  with  coordinate  powers  in  directing  the  policy  and  affairs  of  the 
institute. 

It  is  possible  to  indicate  only  in  outline  and  in  a  general  way  the  principal 
departments  or  divisions  of  an  institute  of  hygiene,  as  details  of  organization 
and  division  of  work  should  be  left  to  the  staff  of  teachers  whose  interests  and 
qualifications  will  very  witli  the  individuals. 

a.  Chemical  Division. — Tlie  applications  of  chemistry  to  sanitar}^  science 
and  art  are  extremely  important  and  varied,  and  already  highly  developed. 

b.  Biological  Division. — Here  there  would  be  a  number  of  subdivisions,  as 
bacteriolog}',  protozoology,  medical  zoology. 

c.  Engineering  or  Physical  Division. — A  part  of  tbis  can  best  be  provided 
for  in  tbe  engineering  school,  but  tbe  institute  should  provide  opportunities 
for  the  study  of  certain  hygienic  problems  requiring  the  application  of 
physical  science. 


INSTITUTE  OF  HYGIENE  667 

d.  Statistical  Division. — While  the  various  questions  connected  with  the 
collection  and  study  of  vital  statistics  constitute  the  most  important  subject 
in  this  field,  there  are  other  important  applications  of  statistical  science  to 
hygiene. 

e.  Division  of  General  Hygiene  and  Preventive  Medicine. — Under  this 
broad  head  may  be  included  epidemiology,  industrial  hygiene,  the  principles 
of  public  health  administration  and  other  subjects  not  embraced  under  the 
previous  captions. 

The  foregoing  classification  is  not  designed  to  be  either  final  or  exhaustive 
and  is  manifestly  reduced  to  its  simplest  terms. 

If  qualified  men  can  be  found  there  should  be  three  or  four  teachers  of  the 
rank  of  full  professors,  but  in  their  absence  it  would  be  better  to  select  even 
for  some  of  the  important  divisions  younger  men  of  great  promise  with  the 
grade  of  assistant  professors  or  of  associates.  In  addition  to  these  probably 
at  least  eight  or  ten  assistants  at  moderate  salaries  would  be  required. 

As  already  stated,  the  institute  once  established  on  its  own  foundation 
will  draw  upon  the  medical  school,  the  engineering  school  and  other  depart- 
ments of  the  university  for  courses  of  instruction  which  it  wall  not  care  to 
provide  on  its  own  grounds,  and  it  will  itself  cooperate  in  furnishing  instruc- 
tion to  students  in  other  departments. 

5.  Field  Work. — Hygienic  excursions  to  inspect  water  filtration  plants, 
sewage  disposal  systems,  methods  of  heating  and  ventilation  and  for  kindred 
purposes  constitute  a  valuable  part  of  practical  sanitary  training.  The  most 
important  training  in  the  field,  however,  will  be  provided  by  establishing 
working  relations  with  state  and  municipal  departments  of  health  and  wnth 
the  United  States  Public  Health  Service.  This  arrangement  wdll  provide 
for  giving  to  the  students  practical  experience  in  every  department  of  public 
health  work.  The  students  may  in  this  way  become  acquainted  under 
favorable  conditions  with  the  methods  of  handling  the  health  problems  of 
the  large  city  as  well  as  those  of  the  rural  conmiunity.  There  will  be  oppor- 
tunity for  participating  in  the  work  of  sanitary  surveys.  Cooperation  with 
the  Federal  Public  Health  Service  will  give  good  opportunity  for  experience 
in  quarantine  work  and  in  sanitary  and  epidemiological  work  on  a  large 
scale.  Such  relations  will  be  mutually  helpful.  The  states  and  cities  will 
reap  the  benefit  of  intelligent  and  scientifically  trained  workers  who  will 
enter  the  service  as  real  workers  in  all  fields  of  its  activities.  The  institute 
and  its  students  in  turn  will  have  the  benefit  of  this  practical  experience. 

6.  Museum. — An  important  feature  of  the  institute  will  be  a  good 
hygienic  museum,  which  will  contain  models,  charts,  preparations,  and  other 
material  which  can  be  gradually  brought  together.  This  will  serve  not  only 
for  demonstrative  teaching,  but  also  for  the  education  of  the  public.    The 


668  INSTITUTE  OF  HYGIENE 

influence  and  usefulness  of  the  institute  ■will  be  extended  by  popular  lectures, 
conferences  and  extension  courses. 

7.  Special  Courses. — The  institute  should  provide  for  the  needs  of  those 
already  engaged  in  health  work,  who  desire  to  pursue  short  courses  or  to  do 
advanced  work  in  special  branches. 

8.  Requirements  for  Admission;  Certificates  and  Degrees. — The  details 
regarding  the  conditions  for  admission  to  the  institute  may  be  left  to  future 
consideration,  but  it  should  be  stated  that  while  the  majority  of  candidates 
for  diplomas  and  degrees  will  doubtless  be  graduates  in  medicine,  these 
distinctions  should  not  be  limited  to  physicians.  The  institute  should  be 
ready  to  receive  and  to  reward  with  its  diplomas  and  degrees  all  who  come 
with  a  satisfactory  preliminary  education  and  pursue  the  required  training, 
which  need  not  be  rigidly  uniform  for  all  matriculates.  Even  those  who 
may  not  meet  the  requirements  for  matriculation  and  become  candidates  for 
the  degree  may  find  opportunity  to  pursue  special  courses  of  study.  It  has 
been  abundantly  demonstrated  that  the  profession  of  public  health  work  can 
be  successfully  followed  by  sanitarians  whose  principal  training  has  been 
sanitary  engineering,  sanitary  chemistry  and  sanitary  biology. 

9.  Influence  of  the  Institute. — The  benefits  to  be  expected  from  tlie  estab- 
lishment of  such  an  institute  as  that  proposed  are  not  to  be  measured  solely 
by  the  number  of  students  trained  mthin  its  walls.  The  institute  can  supply 
only  a  relatively  small  number  of  those  who  desire  to  enter  upon  public 
health  service.  The  far-reaching  infiuence  of  the  institute  should  be  felt  in 
the  advancement  of  the  science  and  the  improvement  of  the  practice  of 
public  health,  in  establishing  higher  standards  and  better  methods  of  profes- 
sional education  in  this  field,  in  stimulating  the  foundation  of  similar  insti- 
tutes in  other  parts  of  the  country,  in  supplying  teachers  and  in  cooperating 
with  schools  of  a  simpler  character  designed  for  briefer  technical  training 
which  should  be  established  in  each  state  in  connection  jointly  with  boards 
of  health  and  medical  schools. 


THE  SCHOOL  OF  HYGIEXE  AND  PUBLIC  HEALTH  AT   THE 
JOHNS  HOPKINS  UNIVEESITY ' 

Our  president,  with  a  self-denial  wliicli  I  might  appreciate,  has  intrusted 
to  me  the  agreeable  function  of  announcing  upon  this  occasion  one  of  the 
most  important  and  gratifying  gifts  ever  bestowed  upon  this  university,  a 
benefaction  likewise  of  national  interest.  This  is  the  provision  of  funds  by 
the  Eockefeller  Foundation  for  the  purpose  of  establishing  in  connection 
with  the  Johns  Hopkins  University  a  school  of  hygiene  and  public  health. 
This  action  of  the  Foundation  was  conununicated  to  the  trustees  of  the 
university  only  today  shortly  before  these  exercises.  It  is  hardly  necessary 
to  add  that  the  trustees  have  acted  promptly  in  accepting  this  generous  gift 
and  have  already  taken  the  first  steps  toward  organization  of  the  new  school 
in  selecting  Dr.  Howell  as  the  head  of  the  physiological  division  of  the  Insti- 
tute of  Hygiene  and  to  cooperate  in  the  work  of  organization  and  develop- 
ment, and  in  appointing  me  as  director. 

It  is  expected  that  the  school  will  be  opened  in  October,  1917,  as  it  is  esti- 
mated that  a  year  will  be  required  for  the  planning,  construction  and  equip- 
ment of  the  building  and  the  gathering  together  of  the  staff  of  teachers. 
The  necessary  funds  for  construction,  equipment,  maintenance  and  expenses 
of  the  school  will  be  provided  by  the  Eockefeller  Foundation. 

When  we  consider  the  revolutionary  discoveries  of  the  last  forty  years  in 
our  knowledge  of  the  causes  and  means  of  prevention  of  diseases,  the  great 
progress  in  the  science  and  art  of  public  health  and  the  incalculable  benefits 
to  the  community  in  the  application  of  this  knowledge,  we  can  all  realize 
the  beneficent  service  rendered  to  this  great  cause  by  this  latest  gift  of  the 
Eockefeller  Foundation,  which  has  already  contributed  so  largely  to  the 
advancement  of  medical  science  and  education.  Not  only  this  university,  but 
also  this  city  and  state  and  the  Avhole  country  owe  a  great  debt  of  gratitude 
to  the  Foundation  for  tbe  provision  thus  made  of  improved  opportunities 
for  training  in  preventive  medicine  and  public  health  work  and  for  cultiva- 
tion of  the  sciences  which  find  application  in  public  and  personal  hygiene. 

It  is  naturally  most  gratifying  to  us  that  Baltimore  and  the  Johns  Hop- 
kins University  have  been  selected  for  the  location  of  the  new  school  of 

*  Report  of  remarks  made  at  the  Commencement  Exercises  of  the  Johns 
Hopkins  University,  June  13,  1916. 

Johns  Hopkins  Univ.  Circ,  Bait.,  1916,  XXXV,  No.  7,  9-13. 

669 


670  SCHOOL  OF  HYGIENE  AND  PUBLIC  HEALTH 

hygiene  and  public  health.  Our  city,  in  its  situation,  its  relations  to  the 
south  and  other  parts  of  the  country,  its  proximity  to  the  national  capital, 
and  its  opportunities  for  study  and  work  in  the  field  of  preventable  diseases, 
is  favorably  located  for  such  a  school.  I  think  that  I  may  say  that  determin- 
ing considerations  have  been  the  advantages  arising  from  close  association  of 
the  school  with  the  medical  school,  the  hospital,  the  school  of  engineering 
and  other  departments  of  the  Johns  Hopkins  University,  and  it  is  for  these 
reasons  especially  that  the  decision  reached  by  the  Foundation  after  pro- 
longed and  careful  study  of  the  situation  in  different  parts  of  the  country 
is  so  gratifying  to  us.  The  wider  extension  of  the  influence  and  usefulness 
of  the  university,  the  possibilities  of  greater  service  to  this  city  and  state  and 
to  the  country  at  large  about  to  be  opened  by  the  new  school,  should  materi- 
ally strengthen  the  position  of  the  Jolms  Hopkins  University  and  aid  in 
securing  much-needed  support  in  the  development  of  other  departments. 

While  the  detailed  plans  of  organization  of  the  school  of  hygiene  and 
public  health  will  be  worked  out  and  announced  later,  a  few  points  may  here 
be  touched  upon. 

Inasmuch  as  the  profession  of  the  sanitarian  and  worker  in  public  health, 
although  closely  connected,  is  not  identical  with  that  of  the  practitioner  of 
medicine ;  the  school  of  hygiene  and  public  health,  while  working  in  coopera- 
tion with  the  medical  school,  as  well  as  with  the  school  of  engineering,  will 
have  an  independent  existence  under  the  university  coordinate  with  these 
schools.  Opportunities  in  each  will  be  available  to  students  of  the  other 
schools. 

The  central  and  principal  feature  of  the  school  will  be  an  institute  of 
hygiene  housed  in  its  own.  building,  provided  with  the  requisite  laboratories 
and  facilities  and  with  its  own  staff  of  teachers  giving  their  entire  time  to  the 
work  of  teaching  and  investigating. 

There  will  be  here  laboratories  of  sanitary  chemistry  of  physiology  as 
applied  to  hygiene — a  most  important  although  much  neglected  subject — 
of  bacteriology  and  protozoology,  and  provision  for  epidemiology,  industrial 
hygiene,  vital  statistics,  a  museum,  library,  etc.  Additional  facilities  for 
instruction  and  research  will  be  supplied  by  the  medical  and  the  engineering 
schools,  the  hospitals,  especially  the  newly  opened  wards  for  infectious  dis- 
eases of  the  Harriet  Lane  Home  for  Invalid  Children,  and  other  departments 
of  the  university,  which  will  be  aided  in  undertaking  the  new  work. 

It  is  anticipated  that  mutually  helpful  relations  will  be  established  with 
our  municipal  and  state  departments  of  health,  assurance  of  which  has  been 
given  by  our  public-spirited  Mayor  and  other  authorities,  and  with  the 
Federal  public  health  service,  whereby  opportunities  will  be  afforded  for  field 


AT  THE  JOHNS  HOPKINS  UNIVERSITY  671 

work  and  other  practical  experience  in  various  branches  of  public  health 
work. 

Especially  advantageous  will  be  the  relations  with  the  International 
Health  Commission  of  the  Rockefeller  Foundation,  which  is  engaged  in  the 
study  and  control  not  only  of  hook-worm,  but  also  of  malaria,  yellow  fever 
and  other  tropical  diseases,  which  will  receive  due  attention  in  the  work  of 
the  Institute. 

It  is  intended  that  the  school  shall  furnish  opportunities  of  a  high  order 
for  the  cultivation  of  the  various  sciences  which  find  application  in  hygiene, 
sanitation  and  preventive  medicine,  and  for  the  training  of  medical  students, 
engineers,  chemists,  biologists  and  others  properly  prepared  who  wish  to  be 
grounded  in  the  principles  of  these  subjects,  and  above  all  for  the  training 
of  those  who  desire  to  fit  themselves  for  careers  in  public  health  work  in  its 
various  branches — that  most  attractive  profession  for  those  qualified  to 
practise  it.  The  most  urgent  need  at  the  present  time  is  provision  for  the 
scientific  training  of  prospective  health  officials  and  for  supplementary  and 
advanced  courses  for  those  already  engaged  in  sanitary  work.  Suitable 
recognition  of  the  satisfactory  completion  of  work  in  the  school  will  be 
given  by  the  bestowal  of  certificates  and  degrees. 

Directions  in  which  it  may  be  expected  that  the  usefulness  of  the  school 
of  hygiene  and  public  health  will  be  extended  are  cooperative  efforts  with 
our  training  school  for  nurses  and  other  agencies  in  the  training  of  public 
health  nurses,  who  have  become  such  important  agents  in  voluntary  and 
public  health  work,  and  in  the  education  of  the  public  by  exhibits,  lectures 
and  other  means  to  a  better  application  and  understanding  of  the  signifi- 
cance and  needs  of  public  and  personal  hygiene. 

The  dreams  which  many  of  us  in  the  medical  faculty  have  long  cherished 
are  now  about  to  be  realized.  The  opportunity  which  this  great  benefaction 
places  in  the  hands  of  the  Johns  Hopkins  University  is  most  inspiring.  It 
is  comparable  to  that  presented  to  the  university  at  its  beginning  for  the 
promotion  of  higher  education,  and  later  to  the  medical  school  and  the 
hospital  for  advancement  of  the  standards  and  methods  of  medical  educa- 
tion. The  responsibilities  devolving  upon  the  university  in  this  new  under- 
taking, entrusted  to  it  with  such  high  hopes,  are  commensurate  with  the 
splendid  opportunities.  May  we  not  confidently  anticipate  that  in  this  new 
field  the  results  will  be  in  keeping  with  the  achievements  of  the  university  in 
the  other  fields  it  has  cultivated  so  successfully  ? 


REMARKS  AT  OPENING  OF  MEDICAL  CONFERENCE  OF  RED 

CROSS  SOCIETIES' 

I  esteem  it  a  very  great  privilege  to  speak  on  behalf  of  my  colleagues  who 
are  delegates  to  this  Conference.  I  think  it  is  not  going  too  far  to  say  that 
the  entire  medical  profession  of  America  and,  indeed,  all  those  who  are 
interested  in  the  prevention  of  disease  and  in  the  promotion  of  public  health, 
would  be  glad  to  express  their  appreciation  to  the  Committee  of  Red  Cross 
Societies  for  having  called  together  this  Conference.  Especially,  I  think  all 
present  will  agree  that  we  are  indebted  to  Mr.  Davison,  who  has  again  added 
to  the  very  great  service  he  has  rendered  in  leading  the  American  Red  Cross 
during  the  war,  by  looking  to  the  future,  and  for  having  conceived  the  idea 
that  the  great  forces,  resources,  energies  and  thoughts  which  have  been 
called  into  action  by  the  Red  Cross  during  the  war,  should  continue  to 
operate  for  the  benefit  of  mankind. 

How  quickly  we  who  have  been  interested  in  these  questions  have  re- 
sponded to  this  invitation!  How  warmly  we  have  welcomed  this  great 
opportunity,  carrying  with  it  an  equally  great  responsibility !  I  think  that 
those  of  us  who  have  often  felt  that  we  have  been  preaching  to  deaf  ears  the 
gospel  of  health  have  come  here  feeling  actual  joy  that  at  last  such  great 
forces  as  are  embodied  in  the  Red  Cross  Associations  are  to  be  strengthened 
and  expanded  into  a  world-wide  organization,  for  the  promotion  of  health 
and  the  prevention  of  disease.  We  are  confident  that  there  are  great  possi- 
bilities of  good  in  the  application  of  this  knowledge  to  the  welfare  of  man- 
kind. 

It  is  a  subject  for  congratulation  that  the  minds  of  men  have  been 
awakened  to  the  possibilities  of  improving  the  health  and  welfare  of  mankind 
through  the  control  of  disease,  and  it  is  a  matter  of  the  utmost  gratification 
that  these  objects  are  to  be  attained  through  the  Red  Cross  whose  organiza- 
tions are  to  be  continued,  strengthened  and  expanded  for  the  good  of  man- 
kind. 

We  wlio  have  been  joined  togctlier  in  close  association  during  this  war  in 
fighting  tlie  common  enemy,  an  enemy  of  civilization,  are  to  continue  in 

*  Report  of  remarks  as  Presiding  Officer  at  the  Second  General  Session  of  the 
Medical  Conference,  held  at  the  invitation  of  the  Committee  of  Red  Cross 
Societies,  Cannes,  France,  April  1,  1919. 

Proc.  Med.  Conf.,  Cannes,  France,   1919,   24-25. 
672 


MEDICAL  CONFERENCE  OF  EED  CROSS  673 

closer  bonds  of  friendship,  because  we  are  joined  together  not  to  forge 
weapons  of  destruction,  but  united  to  consider  what  we  can  contribute  for 
the  healing  of  the  nations.  There  are  assembled  in  Paris  delegates  to  con- 
sider the  formation  of  a  League  of  Nations.  We  are  assembled  here  to  confer 
upon  the  formation  of  a  League  of  Health.  And  I  venture  to  say  that  what 
we  negotiate  here  will  signify  to  mankind  fully  as  much  as  the  result  of  the 
deliberations  in  Paris. 

I  believe  that  we  are  contributing  to  the  good  and  welfare  of  mankind  by 
the  creation  of  this  League  of  Health  under  the  Associated  Red  Cross 
Societies  of  the  World,  quite  as  much  as  will  be  contributed  by  the  League 
of  Nations  under  whose  sanction,  if  not  under  whose  direction,  I  trust  we 
shall  be  permitted  to  act.  We,  therefore,  pledge  the  loyalty  of  our  delegates 
from  America  to  this  Committee  of  Red  Cross  Societies,  and  we  wish  at  the 
same  time  to  express  our  pleasure  at  being  associated  with  our  colleagues 
from  France,  England,  Italy,  and  Japan,  in  this  great  movement. 


SCOPE  OF  THE  PROPOSED  HEALTH  ACTIVITIES  OF  THE 
LEAGUE  OF  RED  CROSS  SOCIETIES ' 

In  our  deliberations  upon  the  general  plan  and  purposes  of  a  central 
health  organization  under  the  associated  national  Red  Cross  Societies,  there 
are  certain  points  which  it  seems  to  me  important  for  us  to  bear  in  mind. 

The  first  consideration  is  the  importance  of  starting  tlie  new  work  along 
the  right  lines.  A  broad,  comprehensive  and  detailed  program  will  doubtless 
eventually  be  developed,  but  this  must  be  a  matter  of  growth,  determined 
by  the  results  of  experience  and  by  the  available  resources.  We  cannot  pre- 
cisely define  or  foresee  these  lines  of  future  development,  although  I  believe 
that  we  are  all  agreed  that  their  possibilities  are  of  incalculable  importance 
for  the  welfare  of  mankind.  Our  more  immediate  task  is  to  make  recom- 
mendations concerning  the  initial  steps  which  should  be  taken,  trusting  that 
time  will  indicate  the  paths  which  subsequently  may  be  followed  to  greatest 
advantage.  The  future  developments  are  obviously  dependent  in  no  small 
measure  upon  the  successful  initiation  of  the  plan  upon  relatively  simple 
lines. 

In  the  second  place,  we  should  keep  in  mind  that  we  have  been  called 
together  to  confer  upon  what  an  association  or  league  of  Red  Cross  Societies 
can  wisely  undertake  in  the  promotion  of  health  and  the  prevention  of  dis- 
ease among  the  peoples  of  the  world.  While  present  conditions  do  not  per- 
mit this  league  to  assume  a  completely  international  character,  it  is  permis- 
sible to  look  forward  to  the  time  when  it  will  possess  this  character,  but  even 
under  existing  circumstances,  we  should  not  lose  sight  of  the  fact  that  our 
recommendations  should  concern  themselves  with  the  activities  of  an  organ- 
ization representative  of  many  countries  of  the  world. 

Inasmuch  as  the  central  organization  will  operate  mainly  through  the 
various  constituent  national  societies,  and  upon  their  invitation,  it  is  clear 
that  a  primary  and  main  purpose  of  this  organization  will  be  to  strengthen 
and  develop  existing  Red  Cross  Societies,  aiding  them  to  enter  upon  these 
new  and  promising  fields  of  work,  and  also  to  create  such  societies  where  tliey 
do  not  now  exist. 

*  Report  of  remarks  as  Presiding  Officer  at  the  Fourth  General  Session  of  the 
Medical  Conference,  Cannes,  France,  April  3,  1919. 
Proc.  Med.  Conf.,  Cannes,  France,  1919,  50-51. 
674 


SCOPE  OF  PROPOSED  HEALTH  ACTIVITIES  675 

It  should  require  little  argument  to  show  that  the  Red  Cross  in  entering 
upon  the  field  of  preventing  human  misery  caused  by  disease  and  suffering,  is 
not  diverting  from  its  great  work  of  relief,  but  is  rather  following  a  natural 
and  logical  path  of  development;  for  preventable  disease  is  a  continuing 
calamity,  and  its  control  is  the  best  kind  of  relief,  which  will  render  unneces- 
sary many  of  the  large  expenditures  and  appeals  assumed  by  the  Red  Cross 
in  the  past. 

Although  public  health  administration  is  in  the  main  a  governmental 
function,  we  all  know  how  helpful  in  manifold  ways  are  voluntary  organiza- 
tions, such  as  those  concerned  with  tuberculosis,  with  child  hygiene,  with 
mental  hygiene,  with  venereal  diseases,  etc.,  in  educating  and  organizing 
public  opinion,  in  carrying  on  demonstrations,  in  influencing  beneficially 
sanitary  legislation  and  administration  and  in  promoting  in  various  other 
ways  modern  health  movement.  The  Red  Cross  will  not  supplant  any  of 
these  agencies,  governmental  or  voluntary,  but  rather  will  aid  them  and 
help  to  coordinate  their  activities. 

It  cannot  fail  to  be  a  source  of  the  utmost  gratification  to  all  interested  in 
the  betterment  of  health  and  the  prevention  of  disease  that  the  Red  Cross, 
with  its  unequaled  influence  and  power,  and  its  record  of  magnificent  work 
in  fields  of  activity  of  the  greatest  importance  is  to  continue  its  labor  in 
times  of  peace  for  the  future  welfare  of  the  world.  That  these  activities  will 
be  guided  by  the  voice  of  science  is  indicated  by  the  character  of  the  Con- 
ference which  we  have  been  summoned  to  attend. 

One  of  the  important  functions  of  the  central  health  bureau  of  the  asso- 
ciated Red  Cross  Societies  will  be  to  collect  and  distribute  for  the  informa- 
tion and  education  of  the  public,  the  best  available  knowledge  concerning 
hygiene  and  methods  of  preventing  disease.  A  survey  of  the  incidence  and 
distribution  of  diesase,  and  the  general  health  conditions  in  the  different 
countries  with  the  methods  of  control  adopted  would  be  an  extremely  helpful 
and  much-needed  contribution. 

The  modern  health  movement  started  in  England  less  than  a  century  ago 
with  such  a  survey,  which  indicated  clearly  that  there  were  controllable 
factors  determining  the  prevalence  of  disease  in  certain  localities,  and  under 
certain  conditions  of  living  and  of  working.  As  a  result,  there  developed  in 
England  a  practice  of  local  public  health  administration  in  which  this 
country  still  leads  the  world.  Besides  England,  each  of  the  countries  repre- 
sented in  this  conference  has  something  of  value  to  contribute.  France,  the 
country  of  Pasteur,  so  worthily  represented  at  this  Conference  by  his  suc- 
cessor and  our  President,  Dr.  Roux,  and  his  colleagues,  has  been  a  leader  in 
scientific  discovery,  and  has  given  us  such  men  unmatched  in  the  power  of 
orderly  thinking  and  clear  expression.    We  owe  to  Italy  studies  of  malaria 


676  SCOPE  OF  PEOPOSED  HEALTH  ACTIVITIES 

and  methods  for  its  control,  of  the  greatest  importance  in  sanitation,  and  it 
is  gratifying  to  find  in  attendance  on  this  Conference  those  who  have  made 
these  great  contributions.  I  had  the  opportunity  four  years  ago  of  becoming 
personally  acquainted  with  the  fruitful  activities  of  scientific  investigation 
in  Japan,  in  her  admirable  institutes.  I  think  that  America,  largely  through 
the  efforts  of  Dr.  Biggs,  may  claim  to  have  had  a  leading  share  in  the  appli- 
cation of  scientific  discoveries  in  public  health  organization  and  adminis- 
tration, and  especially  in  the  organization  and  development  of  public  health 
diaffnostic  laboratories,  which  we  regard  as  a  central  feature  of  our  sanitary 
methods.  I  cite  these  instances  merely  to  illustrate  the,  benefits  which  may 
be  expected  from  a  central  health  organization,  such  as  that  contemplated 
under  the  Eed  Cross,  in  which  the  sanitarians  and  methods  of  the  leading 
civilized  countries  are  represented. 


EERATA 


L.  F.  T. 

means 

line  from  top;  L.  F. 

Page 

Location  of  Error 

12 

L.  F.  T. 

3 

"  cachechtischen  " 

12 

L.  F.  B. 

14 

"  haden  " 

14 

L.  F.  T. 

8 

"  Versuch  " 

24 

L.  F.  B. 

18 

"23" 

28 

L.  F.  B. 

11 

"  OS  " 

34 

L.  F.  B. 

2 

"  eden  " 

54 

L.  F.  T. 

6 

"  then  " 

54 

L.  F.  T. 

7 

"  massed  " 

61 

L.  F.  T. 

8 

"  elestic  " 

61 

L.  F.  T. 

19 

"  lighted  " 

64 

L.  F.  B. 

11 

"  conglutionation  " 

66 

L.  F.  T. 

18 

"  other  " 

68 

L.  F.  T. 

17 

"  statments  " 

81 

L.  F.  B. 

25 

"  an  " 

85 

L.  F.  T. 

3 

"  showing  " 

118 

L.  F.  T. 

6 

"  from  " 

145 

L.  F.  T. 

17 

"  envoloped  " 

154 

L.  F.  B. 

6 

"  enothelium  " 

203 

L.  F.  B. 

12 

"  ligual " 

220 

L.  F.  B. 

17 

"  occurence  " 

222 

L.  F.  T. 

17 

"  gapping  " 

259 

L.  F.  T. 

22 

"  suject  " 

276 

L.  F.  T. 

4 

"  branchial  " 

298 

L.  F.  T. 

17 

"may  " 

303 

L.  F.  T. 

18 

"  system  " 

358 

L.  F.  T. 

3 

"  infectionus  " 

403 

L.  F.  T. 

26 

"  hydroprobia  " 

417 

L.  F.  T. 

19 

"  mucous  " 

418 

L.  F.  B. 

1 

"  lacohol  " 

420 

L.  F.  T. 

10 

"  oedema  " 

446 

L.  F.  T. 

7 

"  sebaseous  " 

449 

L.  F.  B. 

8 

"  boogy  " 

453 

L.  F.  B. 

16 

"  vulvulae  " 

486 

L.  F.  T. 

2 

"  febris  tertanar  " 

506 

L.  F.  B. 

3 

'*  falicipa7-wm  " 

519 

L.  F.  T. 

5 

"  malanotic  " 

530 

L.  F.  T. 

10 

"  pyogenic  " 

536 

L.  F.  B. 

7 

"  Cystirercus  " 

537 

L.  F.  T. 

22 

"  trico-cephalus  " 

539 

L.  F.  T. 

11 

"  Cysticeri  " 

539 

L.  F.  T. 

18 

"  of  dochmius  " 

539 

L.  F.  B. 

19 

"  Ascaris  mystax  " 

B.  means  line  from  bottom 


Correc 

shou 
shou 
shou 
shou 
shou 
shou 
shou 
shou 
shou 
shou 
shou 
shou 
shou 
shou 
shou 
shou 
shou 
shou 
shou 
shou 
shou 
shou 
shou 
shou 
shou 
shou 
shou 
shou 
shou 
shou 
shou 
shou 
shou 
shou 
shou 
shou 
shou 
shou 
shou 
shou 
shou 
shou 


ion 

d  read 
read 
read 
read 
read 
read 
read 
d  read 
d  read 
d  read 
d  read 
d  read 
d  read 
d  read 
d  read 
read 
read 
read 
read 
read 
read 
d  read 
d  read 
d  read 
read 
read 
read 
read 
read 
read 
read 
read 
read 
read 
read 
read 
d  read 
d  read 
d  read 
d  read 
d  read 
d  read 


cachectischen 

haben 

Versuche 

20 

so 

eben 

than 

masses 

elastic 

lighter 

conglutination 

others 

statements 

on 

slowing 

form 

enveloped 

endothelium 

lingual 

occurrence 

gaping 

subject 

brachial 

make 

symptom 

infectious 

hydrophobia 

mucus 

alcohol 

oedema, 

sebaceous 

bogy 

valvulae 

febris  tertianae 

falciparum, 

melanotic 

pyrogenic 

Cysticercus 

trichocephalus 

Cysticerci 

or  Dochmius 

Ascaris  mystax 


677 


6T8 


8 

ERRATA 

Page 

Location  of  Error 

Correction 

540 

L.  F.  T. 

2 

"  drassicollis  " 

should 

read 

crassicollis 

543 

L.  F.  T. 

,t 

"  creditate  " 

should 

read 

crepitate 

551 

L.  F.  B. 

17 

"  definitian  " 

should 

read 

definition 

575 

L.  F.  T. 

18  and  other  pages  "  feces 

"  should 

read 

faeces 

576 

L.  F.  B. 

1 

"  fecal " 

should 

read 

faecal 

577 

L.  F.  B. 

16 

"  remore  " 

should 

read 

remove 

586 

L.  F.  B. 

21 

"  cholera  typhoid  " 

should 

read 

cholera  or  typhoid 

595 

L.  F.  B. 

13 

"  houses  " 

should 

read 

housed 

648 

L.  F.  T. 

18 

"  shore  " 

should 

read 

short 

653 

L.  F.  B. 

1 

"  interested  " 

should 

read 

interpreted 

658 

L.  F.  B. 

1 

"  insanitation  " 

should 

read 

unsanitation 

663 

L.  F.  T. 

19 

"  health  " 

should 

read 

healthy 

666 

L.  F.  B. 

9 

"  very  " 

should 

read 

vary 

670 

L.  F.  B. 

12 

"  chemistry  " 

should 

read 

chemistry, 

UNIVERSITY  OF  CALIFORNIA  LIBRARY 

Los  Angeles 
This  book  is  DUE  on  tlie  last  date  stamped  below. 


APR  1 6  RECD 

'"•'^-^^dcfO'6  1970 
0CT13REC'D 


Form  L9-40ot-5,'67(H2161s8)4939 


riKMVi 


3  1158  00361    5837 


liiilLwJln"^  FACILITY 


^     000  346  566 


■\}j-j,<-\:^r,-c'vxxv.\^%\rj,X3[\-.^^^^^^ 


